SRC TR-13-053

HPV2 TEST RULE DATA ADEQUACY REVIEW (FINAL): 

REPEATED-DOSE, REPRODUCTIVE, AND DEVELOPMENTAL TOXICITY

Acetaldehyde, CASRN 75-07-0

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-W-09-027

Task FG007.3.009.001

Submitted to:

OCSPP/OPPT/RAD (7403M)

U.S. Environmental 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, 2013
Final HPV2 Chemical Data Adequacy Review CASRN 75-07-0

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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 http://www.regulations.gov/#!documentDetail;

D=EPA-HQ-OPPT-2007-0531-0579 as of August 1, 2013). 

The HPV2 test rule requires the following toxicological testing for CASRN 75-07-0: C2

(consisting of acute toxicity to Daphnia and toxicity to algae testing because the log Kow of 

CASRN 75-07-0 is < 4.21) and F2 (reproduction/developmental toxicity screening test). 

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

Detail;D=EPA-HQ-OPPT-2007-0531-0714 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 75-07-0.

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 by AWG on April 5, 2013 are adequate to satisfy the F2 (reproduction/

developmental toxicity) testing requirement for CASRN 75-07-0 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-HQ-OPPT-2007-

0531-0673 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 75-07-0.

 

1 Log Kow = -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 screening test include Celanese, Ltd., The Dow Chemical Company, and Eastman Chemical Company.
Final HPV2 Chemical Data Adequacy Review CASRN 75-07-0

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D. DATA FOR SIDS ENDPOINTS

D-1. Repeated-Dose/Reproductive/Developmental Toxicity

Summary of endpoint: Adequate

Study 1: Combined repeated-dose oral toxicity study with reproduction/developmental toxicity 

screening test in rats (Charlap, 2013a)

Title: A combined 28-day repeated dose oral (drinking water) toxicity study with the 

reproduction/developmental toxicity screening test of acetaldehyde in rats

This study is: Adequate Not Adequate

TEST SUBSTANCE 

Identity: Acetaldehyde, CASRN 75-07-0

Remarks: 99.77% purity; clear, colorless liquid; obtained from Sigma-Aldrich, Milwaukee, WI,

Lot No. SHBB4508V

METHOD

Method/guideline followed: OECD TG 422 (1996)

Test type: Combined Repeated-Dose Toxicity Study with the Reproduction/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 the definitive test weighed 325-380 g (males) and 201-252 g 

(females) and were approximately 10 weeks old at initiation.

Number of animals/sex/dose: 10

Route of administration: Oral – Drinking Water

Vehicle: Reverse osmosis-purified water 

Exposure duration: The rats were exposed to the test item at 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)
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Doses/concentrations tested: 

Range-finding Test1 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 calculated test item doses (mg/kg-bw/day) in the definitive test, based on drinking water 

consumption values (g/kg-bw/day) and target concentrations of the test item (mg/mL), for each 

treatment period were:

Test 

Concentration

Calculated Dose (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 ensure 

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 Chisquare test with Yates’ correction 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 day] 0, unaccountedfor sites, absolute and relative organ weights, clinical pathology values, pre-coital intervals, and 

continuous FOB [functional observational battery] data values were 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).
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Histopathological data and FOB parameters that yield scalar or descriptive data in the test itemtreated 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 2013a, 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 comparisons 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 of test item formulations in the range-finding and definitive tests.

Range-finding Test Procedure:

Groups of female rats (5/group; approximately 9 weeks 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. Clinical signs, body 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 macroscopically. The tongue, 

gingiva, oropharynx, esophagus, and nonglandular forestomach from the control and high-dose 

groups were examined microscopically. 

Definitive 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 F0 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 2013a, p. 31] 

After the mating period, exposure 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 lactation 
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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. F0 males were 

euthanized after completion of the mating period. F0 females were allowed to deliver and rear 

their pups until lactation day 4, when F0 females and their pups were euthanized. F0 females that 

failed to deliver were euthanized on post-mating day or post-cohabitation day 25. Clinical 

pathology measurements (hematology and serum chemistry) were performed at scheduled 

necropsies on 6 F0 rats/sex/group on collected blood samples. Prior to blood collection, all 

males, including those not scheduled for clinical pathology evaluations, were fasted overnight. 

F0 females were not fasted because they were in lactation. The same 6 F0 rats/sex/group were 

evaluated in the neurological tests, which included FOB (functional observational battery) and 

locomotor activity assessments.

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 neutrophil, 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, and 

appearance (including degree of hemolysis, lipemia, and icterus).

Complete necropsies were performed on all F0 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, including 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 nodes [axillary, 

mandibular, and mesenteric], ovaries and oviducts, oropharynx, pancreas, peripheral nerve, 

pituitary gland, prostate gland, salivary gland, seminal vesicles, skeletal muscle, skin with 

mammary 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 

examinations were performed on tissues 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 included the seminal vesicles, 
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coagulating gland, prostate gland, testes with epididymides and vas deferens, ovaries and 

oviducts, uterus, cervix, and vagina. 

Reproduction was evaluated by determining mating, fertility, and copulation/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 (F1 generation) were individually sexed 

on postnatal days (PNDs) 0 and 4 and were subjected to a detailed physical examination and 

weighed on PNDs 1 and 4. F1 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 were based on calculated test item doses:

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:

LOAEL (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) = 321 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 

highest dose tested in F0 female rats.

Results remarks:

Range-finding 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 study 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 HPV2 Chemical Data Adequacy Review CASRN 75-07-0

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< 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-related findings were observed at gross necropsy or in tissues examined

macroscopically and microscopically. 

Definitive Test Results:

All F0 males and F0 females survived until their scheduled necropsies (study day 46 for F0 males 

and lactation day 4 for F0 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 dorsal 

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 F0 males or F0 females. Some statistically significant alterations were observed, 

but these were transient or not dose-related.

Reduced mean water consumption was seen in F0 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 other groups of F0 males or F0 females displayed reduced mean water 

consumption. 

Neurological Analyses:

No test item-related effects were seen in the FOB assessments. Locomotor activity was reduced 

in F0 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, there were no 

statistically significant effects on motor activity in F0 males during the other 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 motor 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:

Analyses of blood samples collected from males and females (6/sex/group) at scheduled 

necropsy (study day 46 for F0 males and lactation day 4 for F0 females) revealed no treatmentrelated 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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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 upper 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 disorganization of the epithelial layers, 

acanthosis, prominence of the stratum granulosum, and formation of proliferative blunted 

epithelial projections and pearls.” [Charlap 2013a, p. 61] This change was not seen in F0 females 

in other dose groups (0, 1, or 3 mg/mL), in any F0 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 

2013b). 

“There were no other test item-related histologic changes. [The] remaining 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 those 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 F0 group male...with 

testicular seminiferous tubule degeneration and epididymal hypospermia and cellular luminal 

debris. In addition, histologic examination of tissues from one 3 mg/mL F0 group male...was 

not performed.” [Charlap 2013a, 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 of gestation was not affected by test 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:

Absolute and relative weights (relative-to-body and relative-to-brain) of reproductive organs, 

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 vesicles, coagulating gland, prostate gland, testes, epididymides, and vas 

deferens in F0 males, and ovaries, oviducts, uterus, cervix, and vagina in F0 females.

F1 Offspring Examinations:

F1 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 survival during PND intervals 0-1, 1-4, or 0-4, offspring bodyweight 
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(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 endpoint values based on mean calculated doses were as follows1:

Systemic Toxicity:

The NOAEL for systemic toxicity in males and females is 363 and 486 mg/kg-bw/day, 

respectively, based on no effects at the highest dose tested. 

Point-of-Contact Effects:

The LOAEL 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 321 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 NOAEL for reproductive toxicity in males and females is 363 and 486 mg/kg-bw/day, 

respectively, based on no effects at the highest dose tested.

Developmental Toxicity:

The NOAEL for developmental toxicity is 486 mg/kg-bw/day, based on no effects at the highest 

dose tested in F0 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 was 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 induces some toxic effects. Because the current study caused 

point-of-contact effects, the maximum dosage 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 estimated, 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 the dose received during the pre-mating period.
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In the current study, the 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; the guideline requires only a minimum of 

14 days of premating exposure. The study does not deviate from the treatment requirements of 

the guideline and dosing 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. 2013a. A combined 28-day repeated-dose oral (drinking water) toxicity study 

with the reproduction/developmental toxicity screening test of acetaldehyde in rats. 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-OPPT-2007-0531-0714 as of July 

25, 2013.

Charlap, J.H. 2013b. A dosage range-finding 10-day oral (drinking water) toxicity study of 

acetaldehyde in rats. Study No. WIL-876001. 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-HQOPPT-2007-0531-0714 as of July 25, 2013.

Freer, S.D. 2013. An analytical method validation, compatibility, and stability study of 

acetaldehyde in deionized water. Study No. WIL-876002. 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-OPPT-2007-0531-0714 as of July 25, 2013.

Text in quotes is taken directly from Charlap (2013a).