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HPV2 TEST RULE DATA ADEQUACY REVIEW ( FINAL ) : REPEATED

- DOSE, REPRODUCTIVE, AND DEVELOPMENTAL TO XICITY

Acetaldehyde , CASRN 75

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Prepared by: Amy Nguyen , Lisa Ingerman, William Richards, and Teresa Manyin

Defense and Environmental Solutions Division

SRC, Inc. 7502 Round Pond Road North Syracuse, NY 13212

Contract No. EP

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- 027 Task FG007.3 .009.001

Submitted to: OCSPP/OPPT/RAD (7403M) U.S. E nvironmental Protection Agency 1200 Pennsylvania Avenue Washington, D.C. 20460 Bryan Lobar, Project Officer David Brooks, Work Assignment Manager Amy Benson, Alternate Work Assignment Manager

August 1 , 2013Final HPV 2 Chemical Data Adequacy Review CAS RN 75
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1 A. SOURCE MATERIAL USED FOR ASSESSMENT
This document evaluates a submission from the Acetaldehyde Working Group (AWG) , dated April 5 , 2013 , that includes data from toxicity testing of acetaldehyde (CASRN 75

- 07

- 0 ). These data were received by EPA in response to the final test rule, “Testing of Certain High Production Volume Chemicals; Second Group of Chemicals” (76 FR 1067, January 7, 2011; referred to herein as HPV2; available online at htt p://www.regulations.g ov/#!documentDetail; D=EPA

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- 0579 as of August 1 , 2013). The HPV2 test rule requires the following toxicological testing for CASRN 75

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- 0 : C 2 (consisting of acute toxicity to Daphnia and toxicity to algae testing because the log K ow of CASRN 75

- 07

- 0 is < 4.2 1 ) and F2 ( reproduction/developmental toxicity screening test )

. In its April 5, 2013 submission (available online at http://www.regulations.gov/#!document Detail;D=EPA

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- 0714 as of August 1 , 2013), AWG supplied data from a combined repeated

- dose toxicity study with the reproduction/developmental toxicity screening test conducted with CASRN 75

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. 2 These newly submitted data are evaluated for adequacy herein. No other toxicity data are evaluated in this report. B. EVALUATING DATA ADEQUACY The submitted data are evaluated for adequacy in Section D. The study was summarized according to a standard format and assigned a Klimisch reliability code based on its scientific merit and conduct, using professional judgment. To determine whether data were adequate to satisfy SIDS endpoints, study details were compared to current standard test guidelines to establish whether the study met current testing requirements. C. SUMMARY OF DATA ADEQUACY FOR TESTING REQUIRED BY TEST RULE
Data submitted b y AWG on April 5, 2013 are adequate to satisfy the F2 ( reproduction/ developmental toxicity ) testing requirement for CASRN 75

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- 0 promulgated in the final HPV2 test rule. Data previously submitted by AWG for the acute daphnid and algae endpoints on May 18, 2012 (available online at http://www.regulations.gov/#!documentDetail;D=EPA

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- 0673 as of August 1, 2013) were considered adequate to satisfy the C2 testing requirement. There are no outstanding HPV test rule requirements for toxicity testing of CASRN 75

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.

1 Log K ow = - 0.34; value obtained from Hazardous Substance Databank (HSDB). Available online at http://toxnet.nlm.nih.gov/cgi

- bin/sis/htmlgen?HSDB as of August 1, 2013. 2 AWG members that sponsored the combined repeated

- dose toxicity study with the reproduction/developmental toxicity sc reening test include Celanese, Ltd., The Dow Chemical Company, and Eastman Chemical Company.Final HPV 2 Chemical Data Adequacy Review CAS RN 75
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2 D . DATA FOR SIDS ENDPOINTS
D
- 1 . Repeated
- Dose /Reproductive/Developmental Toxicity Summary of endp oint: Adequate Study 1 : C

ombined repeated

- dose oral toxicity study with reproduction/developmental toxicity screening test in rats ( Charlap , 2013 a )
Title: A c ombine d 28

- day repeated dose oral (drinking w ater) t oxicity s tudy with the r eproduction/ d evelopmental t oxicity s creening t est of a cetaldehyde in r ats This study is : Adequate Not Adequate
TEST SUBSTANCE Identity : Acetaldehyde , CAS RN 75

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Remarks: 99.77% purity; clear, colorless liquid ; obtained from Sigma

- Aldrich, Milwaukee, WI , Lot No. SHBB4508V
METHOD Method/guideline followed: O ECD TG 422 (1996) Test type: Combined Repeated

- Dose Toxicity Study with the Reproducti on /Developmental Toxicity Screening Test GLP compliant?: Yes Year study performed: 2012 Test species: Sprague

- Dawley rats [ Crl:CD(SD) ] from Charles River Laboratories, Raleigh , North Carolina

. Rats used in th e definitive test weighed 325

- 380 g (males) and 20 1

- 252 g (females) and were approximately 10 weeks old at initiation.
Number of animals/sex/dose: 1 0
Route of administration: Oral

– Drinking Water
Vehicle: Reverse osmosis

- purified w ater Exposure duration: The rats were exposed to the test item a t a constant concentration (mg/mL) in the drinking water; Males : 47 consecutive days; Females: 54

- 62 consecutive days (females with no evidence of mating or that failed to deliver were exposed for 54

- 67 consecutive days)Final HPV 2 Chemical Data Adequacy Review CAS RN 75
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3 Doses/concentrations tested: Range

- f inding Test 1 Concentrations : 0, 1, 2, 3, 4, or 5 mg/mL (nominal concentrations) ; mean calculated test item doses based on drinking water consumption values (g/kg

- bw/day) and target concentrations of the test item (mg/mL) were 0, 191, 316, 394, 448, and 589 mg/kg

- bw/day. Definitive Test Concentrations : 0, 1 , 3, or 5 mg/mL (nominal concentrations) , based on the range

- finding test in which no clear, toxicologically

- relevant effects were seen at the highest concentration of 5 mg/mL (equivalent to 589 mg/kg

- bw/day)
Mean c alculated test item doses (mg/kg

- bw/day) in the definitive test , based on drinking water consumption values (g/kg

- bw/day) and target concentration s of the test item (mg/mL), for each treatment period were:

Test Concentration Calculated Dos e (mg/kg
- bw/day)

Males Females Treatment Period Entire Treatment Period Prior to Mating Gestation Lactation 1 mg/mL 99 115 121 170 3 mg/mL 239 321 329 465 5 mg/mL 363 486 518 729 During the study, drinking water formulations were 90 to 110% of target concentrations (1, 3, and 5 mg/mL) with some exceptions. Dosing formulations prepared on the eighth day of treatment (1, 3, and 5 mg/mL) and the thirteenth day of treatment (1 mg/mL) were below 90% (range: 75.8% to 88.9% of target concentrations). Therefore, animals were dosed for two weeks longer than planned during the premating period (total of 28 days premating exposure) to ensu re exposure to the correct dosages for at least two weeks prior to mating, as required by OECD TG 422.
Statistical methods used: “Parental mating, fertility, conception, and copulation indices were analyzed using the Chi

square test with Yates’ correcti on factor (Hollander and Wolfe, 1999). Parental body weights (daily, gestation, and lactation), body weight changes, and food and water consumption, offspring body weights and body weight changes, gestation length, numbers of implantation sites and corpora lutea, number of pups born, live litter size on PND [postnatal d ay] 0, unaccounted

for sites, absolute and relative organ weights, clinical pathology values, pre

- coital intervals, and continuous FOB [functional observational battery] data values we re subjected to a parametric one
- way ANOVA [ Analysis of Variance ] (Snedecor and Cochran, 1980) to determine intergroup differences. If the ANOVA revealed significant (p<0.05) intergroup variance, Dunnett's test (Dunnett, 1964) was used to compare the test item

- treated groups to the control group.

1 The 10

- day range

- finding test, briefly reviewed herein, is described in a separate study report ( Charlap 2013b )

.Final HPV 2 Chemical Data Adequacy Review CAS RN 75
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4 Histopathological data and FOB parameters that yield scalar or descriptive data in the test item

treated groups were compared to the control group using Fisher’s Exact test (Steel and Torrie, 1980). Mean litter proportions (percent per litter) of males at birth and postnatal survival were subjected to the Kruskal

- Wallis nonparametric ANOVA (Kruskal and Wallis, 1952) to determine intergroup differences. If the ANOVA revealed significant (p<0.05) intergroup variance, Dunn’s test (Dunn, 1964) was used to compare the test item

- treated groups to the control group. ” [Charlap 2013 a , p. 45

- 46 ] The litter was used as the experimental unit for statistical analyses of offspring data where applicable.
SAS version 9.2 was employed for the remainder of the statistical analyses, including those examining locomotor activity with Repeated Measures Analysis of Variance (RMANOVA) , dose

- response relationships using linear trend tests, and pairwise c omparisons between dose groups using RMANOVA.
Test method/conditions remarks: The test item was stored refrigerated under nitrogen and was considered stable under these conditions. A previous analytical method validation study (Freer 2013) found the test item formulations to be stable at concentrations of 1 to 5 mg/mL (in reverse osmosis

- purified water) at room temperature for 48 hours in glass containers and for 72 hours in plastic drinking water bottles. Therefore, these conditions were used for storage and administration o f test item formulations in the range
- finding and definitive test s
. Range

- f inding Test Procedure: Groups of female r ats (5/group; approximately 9 w ee ks old ; 180

- 236 grams ) were exposed to the test item in their drinking water ad libitum at concentrations of 0 (vehicle only), 1, 2, 3, 4 , or 5 mg/mL for 10 consecutive days. All rats were observed for survival and moribundity twice daily. C linical signs , b ody weights, food consumption, and water consumption were recorded daily for all rats. The rats were sacrificed on study day 10 and examined by necropsy. Selected organs and tissues (external surface, all orifices, external brain surface, and the cranial, thoracic, abdominal, and pelvic cavities, including viscera) were examined macr oscopically . The tongue, gingiva, oropharynx, esophagus, and nonglandular forestomach from the control and high

- dose groups were examined microscopically

. D efinitive Test Procedure: Groups of sexually mature rats (10/sex /group ) were exposed to the test item in their drinking water ad libitum at concentrations of 0 (vehicle only), 1, 3, or 5 mg/mL. Samples of the test item formulations were collected throughout the study and analyzed by high performance liquid chromatography with ultraviolet detection (HPLC/UV) to verify concentrations.

“ Due to dose formulation concentrations being outside of the WIL Research SOP range for acceptance, the vehicle and test drinking water were offered to F 0 males and females ad libitum for 28 consecutive days prior to mating [rather than the planned 14 days] to ensure that the animals received the proper number of doses at acceptable concentrations to satisfy the guideline requirements” [Charlap 2013 a , p. 31] After the mating period, expo sure continued in males until the day of euthanasia, for a total of 47 consecutive days of exposure. Females continued to receive the test substance through lactationFinal HPV 2 Chemical Data Adequacy Review CAS RN 75
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5 day 4, for a total of 54

- 62 consecutive days. Females displaying no signs of mating or that failed to deliver were exposed for 54

- 67 consecutive days. Rats were observed twice daily for mortality and moribundity. Clinical observations, body weights, and food and water consumption were recorded throughout the study. F 0 males were euthanize d after completion of the mating period. F 0 females were allowed to deliver and rear their pups until lactation day 4, when F 0 females and their pups were euthanized. F 0 females that failed to deliver were euthanized on post

- mating day or post

- cohabitati on day 25. Clinical pathology measurements (hematology and serum chemistry) were performed at scheduled necropsies on 6 F 0 rats/sex/group on collected blood samples

. Prior to blood collection, all males, including those not scheduled for clinical patholo gy evaluations, were fasted overnight. F 0 females were not fasted because they were in lactation. The same 6 F 0 rats/sex/group were evaluated in the n eurological tests, which included FOB (functional observational battery) and locomotor activity a ssessments

. Hematological parameters that were evaluated included the following: total leukocyte count , erythrocyte count, hemoglobin , hematocrit , mean corpuscular volume , mean corpuscular hemoglobin , mean corpuscular hemoglobin concentration , platelet count , prothrombin time, activated partial thromboplastin time , reticulocyte count ( percent and absolute ), mean platelet volume , red cell distribution width , hemoglobin distribution width , differential leukocyte count ( percent and absolute ; including neutr ophil , lymphocyte , monocyte , eosinophil, basophil , and large unstained cell), platelet estimate , and red cell morphology

. Serum chemistry parameters that were evaluated included the following: albumin , total protein , globulin , albumin/globulin ratio , total bilirubin, urea nitrogen , creatinine , alkaline phosphatase , alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase , glucose , total cholesterol , calcium , chloride , phosphorus , potassium , sodium , triglycerides, bile acids , an d appearance (including degree of hemolysis, lipemia, and icterus). Complete necropsies were performed on all F 0 animals and selected organs were weighed. Organ weights were recorded for the adrenal glands, brain, epididymides, heart, kidneys, liver, ovaries with oviducts, spleen, testes, thymus gland, and thyroids with parathyroids. Necropsies included an examination of the animal’s external surface, all orifices, external brain surface, and the cranial, thoracic, abdominal, and pelvic cavities, incl uding viscera. Selected tissues (including adrenal glands , aorta , bone with marrow , brain , coagulating glands , eyes with optic nerve , gastrointestinal tract [ esophagus , stomach , duodenum , jejunum , ileum , cecum , colon , and rectum ], gingiva , heart , kidneys , liver , lungs [ including bronchi ] , lymph node s [ axillary , mandibular , and mesenteric ], ovaries and oviducts , oropharynx , pancreas , peripheral nerve , pituitary gland , prostate gland , salivary gland, seminal vesicles , skeletal muscle, skin with m ammary gland , spinal cord , spleen , testes with epididymides and vas deferens , thymus gland , thyroids [with parathyroids ] , tongue , trachea , urinary bladder , uterus with cervix and vagina , and all gross lesions) were collected and preserved for microscopic examination

. Microscopic examination s were performed on t issues from all animals in the control and 5 mg/mL groups. In addition, gross lesions from all animals in all groups were examined microscopically. Reproductive organs that were microscopically examined inclu ded the seminal vesicle s ,Final HPV 2 Chemical Data Adequacy Review CAS RN 75
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6 coagulating gland, prostate gland, testes with epididymides and vas deferens, ovaries and oviducts, uterus, cervix, and vagina.
R eproduction was evaluated by determining mating, fertility, and c opulation/conception indices. Reproductive indices were calculated for each group based on evidence of mating, male success in siring a litter, and the numbers of confirmed pregnancies. Litters were examined daily for survival and changes in appearance or behavior. Pups (F 1 generation) were individually sexed on postnatal days (PNDs) 0 and 4 and were subjected to a detailed physical examination and weighed on PND s 1 and 4. F 1 pups found dead were necropsied; surviving pups were euthanized and discarded (without examination , i.e., without necropsy ) on PND 4.
RESULTS Endpoint value(s) 1 : Definitive Test : The following endpoint values we re based on calculated test item dose s: Systemic Toxicity: NOAEL ( male and female , systemic toxicity ) = 363 and 486 mg/kg

- bw/day for males and females , respectively, based on no effects at the highest dose tested

. Point

- of

- Contact Effects: L OAEL ( female , point

- of

- contact effects) = 486 mg /kg

- bw/day based on minimal to mild epithelial hyperplasia of the caudal palate (gingiva level VI) in female rats; NOAEL ( female , point

- of

- contact effects) = 3 21 mg /kg

- bw/day

. NOAEL ( male , point

- of

- contact effects) = 363 mg/kg

- bw/day , based on no effects at the highest dose tested. Reproductive Toxicity: NOAEL ( male and female , reproductive toxicity) = 363 and 486 mg/kg

- bw/day for males and females , respectively, based on no effects at the highest dose tested

. Developmental Toxicity: NOAEL (developmental toxicity) = 486 mg/kg

- bw/day, respectively, based on no effects at the hi ghest dose tested in F 0 female rats

. Results remarks: Range

- f inding Test Results: All rats survived until scheduled sacrifice on study day 10. Clinical findings, which were observed at similar frequencies in the control group and treated groups , did not appear to be dose

- related, included hair loss on the forelimbs. No other clinical signs were observed. Mean body weight, body weight gain, and food consumption were similar among the treated and control groups. Mean water consumption (for the s tudy interval days 0

- 10) was significantly (p

1 Endpoint values for females were assigned based on the most conservative value from among the mean calculated dosages during pre

- mating, gestation, and lactation periods . In each case, the most conservative value corresponded to the dose received during the pre

- mating period.Final HPV 2 Chemical Data Adequacy Review CAS RN 75
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7 < 0.01) reduced at 3 mg/mL and above . The study author concluded that reduced water consumption was not treatment

- related due to higher than expected water consumption and possible water spillage in the lower dose (1 and 2 mg/L) groups and control group , but this conclusion is not fully supported by the information provided in the report ; therefore , the reduced water consumption at ≥ 3 mg/L cannot be dismissed as unrelated to treatment

. No treatment

- rela ted findings were observed at gross necropsy or in tissues examined macroscopically and microscopically. Definitive Test Results: All F 0 males and F 0 females survived until their scheduled necropsies (study day 46 for F 0 males and lactation day 4 for F 0 females). No treatment

- related clinical findings were observed during weekly physical examinations. Clinical findings, which were also seen in the control group, occurred infrequently and included hair loss on various body surfaces and scabbing on the d orsal head region. These findings did not appear to be related to test item exposure. Body Weight and Food /Water Consumption: No treatment

- related effects on mean body weight , body weight change , or food consumption were observed in F 0 males or F 0 females. Some statistically significant alterations were observed, but these were transient or not dose

- related.
Reduced mean water consumption was seen in F 0 males in the 5 mg/mL group compared with the male control group throughout the study. This finding appeared to be due to palatability of the test water , rather than a toxicological effect . Reduced water consumption in this group was not associated with other measurements, including body weight /body weight change or food consumption

. No ot her groups of F 0 males or F 0 females display ed reduced mean water consumption

. Neurological Analyses: No test item

- related effects were seen in the FOB a ssessments

. Locom otor activity was reduced in F 0 males during some of the timed intervals in the 5 mg/mL group (21

- 30 minute subinterval) and in the 1, 3, and 5 mg/mL groups (31

- 40 minute subinterval). However, t here were no statistically significant effects on motor activity in F 0 males during the oth er timed intervals (i.e., 0

- 10, 11

- 20, 41

- 50, and 51

- 60 minutes) in the same experiment or for the combined analysis including all six timed intervals. There were no changes in m otor activity in test item

- exposed females

. The biological significance of the effects on motor activity in males is unclear since the effects occurred during only some of the timed intervals. Hematology and Clinical Chemistry Measurements : Analys e s of blood samples collected from males and females (6/sex/group) at scheduled necropsy (study day 46 for F 0 males and lactation day 4 for F 0 females) revealed no treatment

related effects on hematology or clinical chemistry parameters. Organ Weights and Pathology: There were no treatment

- related changes in absolute organ weights or relative organ weights ( as related to final body weight or brain weight). Macroscopic examination showed no exposure
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8 related abnormalities of the external body surface, orifices, external surface of the brain, or in the cranial, thoracic, abdominal, or pelvic cavities

.

“ Test item

- related microscopic findings were noted in the uppe r gingiva of the 5 mg/mL group females. Six levels of upper gingiva were examined (Levels I to VI, rostral to caudal). Minimal to mild epithelial hyperplasia of the central palate region was noted in the caudal most gingival section examined (Level VI) [in 3 of 10 females]

. The hyperplasia was characterized by focal to focally extensive thickening of the palate epithelium with disorganiz ation of the epithelial layers, acanthosis, prominence of the stratum granulosum, and formation of proliferative blunted epithelial projections and pearls. ” [Charlap 2013 a , p. 61] This change was not seen in F 0 females in other dose groups ( 0, 1 , or 3 mg/mL), in any F 0 males ( 0, 1, 3, or 5 mg/mL) , or at any dose level (0, 1, 2, 3, 4, or 5 mg/mL) in females treated in the 10

- day range
- finding test (Charlap 2013 b )

.

“ There were no other test item

- related histologic changes. [The] r emaining histologic changes were considered to be incidental findings or related to some aspect of experimental manipulation other than exposure [to] the test item. There was no test item

- related alteration in the prevalence, severity, or histologic character of t hose incidental tissue alterations. There were no histologic changes noted in the reduced fertility (nongravid) females or their male breeding pairs that would have affected reproductive performance with the exception of one control F 0 group male

... with tes ticular seminiferous tubule degeneration and epididymal hypospermia and cellular luminal debris. In addition, histologic examination of tissues from one 3 mg/mL F 0 group male... was not performed. ” [Charlap 2013 a , p. 62] Mating, Fertility, and Gestation: No effects on reproductive performance were observed in males or females. Mating (males or females with evidence of mating) and fertility (males or females that sired a litter or were pregnant, respectively) indices were unaffected by test item exposure

. Other reproductive parameters that were examined and were not affected included the male copulation index, female conception index, and the precoital interval (number of days between pairing and coitus). The mean length o f gestation was not affected by t est item exposure , and there were no effects on the mean numbers of implantation sites, unaccounted

- for sites, corpora lutea, or pups born per female. Necropsy of Reproductive Organs: A bsolute and relative weights ( relative

- to

- body and relative

- to

- brain ) of reproductive organ s, including the testes, epididymides, and ovaries/oviducts , were not affected by test item exposure

. No histopathological findings were seen in the reproductive organs examined microscopically, including the seminal vesicle s , coagula ting gland, prostate gland, testes, epididymides, and vas deferens in F 0 males, and ovaries, oviducts, uterus, cervix, and vagina in F 0 females.
F 1 Offspring Examinations: F 1 pups showed no adverse clinical signs related to test item exposure. Examinations of pups during the postnatal period found no treatment

- related effects on the number of pups per litter, the percentage of males per litter, live litter size, postnatal survival on PND 0 (relative to the number born), postnatal su rvival during PND intervals 0

- 1, 1

- 4, or 0

- 4, offspring bodyweightFinal HPV 2 Chemical Data Adequacy Review CAS RN 75
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9 (PND 1 or PND 4), or offspring bodyweight change (PND 1

- 4). Necropsy of pups found dead during the postnatal period found no treatment

- related effects.
CONCLUSIONS
Definitive test e ndpoint values based on mean calculated doses were as follows 1 : Systemic Toxicity: The N OAEL for systemic toxicity in males and females is 363 and 486 mg/kg

- bw/day, respectively, based on no effects at the hig h est dose tested

. Point

- of

- Contact Effects: The L OAEL for point

- of

- contact effects in females is 486 mg /kg

- bw/day , based on minimal to mild epithelial hyperplasia of the caudal palate (gingiva level VI) in female rats . The NOAEL for point

- of

- contact effects in females is 3 21 mg/kg

- bw/day

. The NOAEL for point

- of

- contact effects in males is 363 mg/kg

- bw/day , based on no effects at the highest dose tested

. Reproductive Toxicity: The N OAEL for reproductive toxicity in males and females is 363 and 486 mg/kg

- bw/day, respectively, based on no effects at the hi ghest dose tested

. Developmental Toxicity: The N OAEL for developmental toxicity is 486 mg/kg

- bw/day , based on no effects at the highest dose tested in F 0 female rats

. STUDY RELIABILITY [2] Reliable with restrictions. The study report did not include a rationale for choosing 5 mg/mL as the maximum test concentration

. In the 10

- day range

- finding study , which was identified as the basis for dose selection , there w as no toxicity at the highest test concentration of 5 mg/mL (equivalent to 589 mg/kg

- bw/day)

. OECD TG 422 recommends testing a range of doses , where the highest dose chosen is one that induce s some t oxic effects. B ecause the current study caused point

- of

- contact effects, the maximum dos age achieved is acceptable. The route of administration of the test substance (via drinking water) did not result in a constant dose throughout the study. The actual doses received by animals fluctuated during the exposure period. Therefore, the endpoint values are expressed as est imated, mean dosages and the most conservative dosage value (from the pre

- mating period) is used as the endpoint value for females.

1 Endpoint values for females were assigned based on the most conservative value from among the mean calculated dosages during pre

- mating, gestation, and lactation periods . In each case, the most conservative value corresponded to t he dose received during the pre

- mating period.Final HPV 2 Chemical Data Adequacy Review CAS RN 75
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10 In the current study, t he animals were dosed for 28 days rather than the planned 14 days (because some of the prepared test formulations were less than 90%). OECD TG 422 does not indicate a maximum duration for the premating exposure period ; t he guideline requires only a minimum of 14 days of premating exposure

. The study does not deviate from th e treatment requirements of t he guideline and d osing of the animals for 28 days is not anticipated to impact the results of the study. Therefore, the exposure period is considered acceptable. REFERENCES Charlap , J.H

. 2013 a
. A c ombined 28

- d ay r epeated

- d ose o ral ( d rinking w ater) t oxicity s tudy with the r eproduction/ d evelopmental t oxicity s creening t est of a cetaldehyde in r ats

. Study No. WIL

- 876003 . Performing Laboratory: WIL Research , Ashland, OH

. Sponsor: Acetaldehyde Working Group of the Vinyl Acetate Council, Inc. , Washington, DC

. Study report available at http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

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- 0714 as of July 2 5 , 2013. Charlap, J.H. 2013 b

. A d osage range
- finding 10

- d ay o ral ( d rinking w ater) t oxicity study of a cetaldehyde in r ats

. Study No. WIL

- 876001 . Performing Laboratory: WIL Research , Ashland, OH. Sponsor: Acetaldehyde Working Group of the Vinyl Acetate Council, Inc. , Washington, DC. S tudy report available at http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

OPPT

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- 0714 as of July 2 5 , 2013. Freer, S.D. 2013. An a nalytical method v alidation, c ompatibility, and s tability study of acetaldehyde in deionized w ater

. Study No. WIL

- 87600 2 . Performing Laboratory: WIL Research , Ashland, OH. Sponsor: Acetaldehyde Working Group of the Vinyl Acetate Council, Inc. , Washington, DC. Study repo rt available at http://www.regulations.gov/#!documentDetail; D=EPA

- HQ

- OPPT

- 2007

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- 0714 as of July 2 5 , 2013. Text in quotes is taken directly from Charlap ( 2013 a ).