20096 Federal Register / Vol. 63, No. 78 /Thursday, April 23, 1998 /Rules and Regulations

(vi) A pipeline must post notices of

operational flow orders, critical periods,

and other critical notices on its Internet

web site and must notify affected parties

of such notices in either of the following

ways to be chosen by the affected party:

Internet E-Mail or direct notification to

the party’s Internet URL address.

[FR Doc. 98–10685 Filed 4–22–98; 8:45 am]

BILLING CODE 6717–01–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 74

[Docket No. 95C–0399]

Listing of Color Additives for Coloring

Sutures; D&C Violet No. 2

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending the

color additive regulations to provide for

the safe use of D&C Violet No. 2 as a

color additive in glycolide/dioxanone/

trimethylene carbonate tripolymer

absorbable sutures for general surgery.

This action responds to a petition filed

by United States Surgical Corp.

DATES: This regulation is effective May

27, 1998; except as to any provisions

that may be stayed by the filing of

proper objections; written objections

and requests for a hearing by May 26,

1998.

ADDRESSES: Submit written objections to

the Dockets Management Branch (HFA–

305), Food and Drug Administration,

12420 Parklawn Dr., rm. 1–23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Ellen M. Waldron, Center for Food

Safety and Applied Nutrition (HFS–

215), 200 C St. SW., Washington, DC

20204, 202–418–3089.

SUPPLEMENTARY INFORMATION:

I. Introduction

In a notice published in the Federal

Register of October 23, 1995 (60 FR

54379), FDA announced that a color

additive petition (CAP 5C0248) had

been filed by United States Surgical

Corp., 150 Glover Ave., Norwalk, CT

06856. The petition proposed to amend

the color additive regulations in

§ 74.3602 D&C Violet No. 2 (21 CFR

74.3602) to provide for the safe use of

D&C Violet No. 2 as a color additive in

glycolide/dioxanone/trimethylene

carbonate tripolymer absorbable sutures

for general surgery. The petition was

filed under section 721(d)(1) of the

Federal Food, Drug, and Cosmetic Act

(the act) (21 U.S.C. 379e(d)(1)).

II. Regulatory History

The regulatory history of D&C Violet

No. 2 was summarized in a final rule

published in the Federal Register of

May 7, 1990 (55 FR 18865). Since the

publication of the May 7, 1990, final

rule, other uses of D&C Violet No. 2

have been approved by the agency. For

example, in a final rule published in the

Federal Register on March 14, 1994 (59

FR 11718), FDA amended § 74.3602 to

list D&C Violet No. 2 for use to color

poly(ε-caprolactone) absorbable sutures

for use in general surgery.

III. Applicability of the Act

With the passage of the Medical

Device Amendments of 1976 (Pub. L.

94–295), Congress mandated the listing

of color additives for use in medical

devices when the color additive in the

device comes into direct contact with

the body for a significant period of time

(section 721(a) of the act). D&C Violet

No. 2 is added to glycolide/dioxanone/

trimethylene carbonate tripolymer

absorbable sutures in such a way that at

least some of the color additive will

come into contact with the body when

the sutures are in place. In addition, the

sutures are intended to be absorbed by

the body, and during the absorption, the

color additive will be deposited in body

tissue. Thus, the color additive will be

in direct contact with the body for a

significant period of time.

Consequently, the petitioned use of the

color additive is subject to the statutory

listing requirement.

IV. The Color Additive

D&C Violet No. 2 is principally 1-

hydroxy-4-[(4-methylphenyl)amino]-

9,10-anthracenedione (CAS Reg. No. 81–

48–1). It is manufactured by either

condensation of quinizarin with ptoluidine or by condensation of 1-

hydroxy-halogenoanthroquinone with

p-toluidine. Because no chemical

reaction consumes all the starting

materials and yields only the desired

product, both the resulting reaction

mixture and commercial product will

contain residual amounts of the starting

materials, including p-toluidine. This

fact is significant because Weisburger et

al., have demonstrated that p-toluidine

is a carcinogen in the mouse (Ref. 1).

Residual amounts of reactants, such

as p-toluidine, and manufacturing aids

are commonly found as impurities in

chemical products, including color

additives.

V. Determination of Safety

Under the general safety clause of the

act (section 721(b)(4) of the act) for color

additives, a color additive cannot be

listed for a particular use unless a fair

evaluation of the data available to FDA

establishes that the color additive is safe

for that use. FDA’s color additive

regulations (21 CFR 70.3(i)) define

‘‘safe’’ as ‘‘reasonable certainty that no

harm will result from the intended use

of the color additive.’’

The color additives anticancer, or

Delaney, clause of the color additive

amendments (section 721(b)(5)(B) of the

act) provides that no noningested color

additive shall be deemed safe and shall

be listed if, after tests that are

appropriate for evaluating the safety of

the additive for such use, it is found to

induce cancer in man or animal.

Importantly, however, the Delaney

clause applies to the additive itself and

not to impurities in the additive. That

is, where an additive itself has not been

shown to cause cancer, but contains a

carcinogenic impurity, the additive is

properly evaluated under the general

safety standard using risk assessment

procedures to determine whether there

is reasonable certainty that no harm will

result from the proposed use of the

additive (Scott v. FDA, 728 F.2d 322

(6th Cir. 1984)).

VI. Safety of the Petitioned Use of the

Additive

FDA estimates that the petitioned use

of the additive, D&C Violet No. 2, will

result in exposure to no greater than 3.8

milligrams per person over a 70-year

lifetime or an estimated daily intake

(EDI) of 0.15 microgram per person per

day (/p/d) (Ref. 2).

FDA does not ordinarily consider

chronic toxicological studies to be

necessary to determine the safety of an

additive whose use will result in such

low exposure levels (Ref. 3), and the

agency has not required such testing

here. However, the agency has reviewed

the available toxicological data on the

additive and concludes that the

estimated small daily intake resulting

from the proposed use of this additive

is safe.

FDA has evaluated the safety of this

additive under the general safety

standard, considering all available data

and using risk assessment procedures to

estimate the upper-bound limit of

lifetime human risk presented by ptoluidine, the carcinogenic chemical

that may be present as an impurity in

the additive. The risk evaluation of ptoluidine has two aspects: (1)

Assessment of exposure to the impurity

from the proposed use of the additive,
Federal Register / Vol. 63, No. 78 /Thursday, April 23, 1998 /Rules and Regulations 20097

and (2) extrapolation of the risk

observed in the animal bioassay to the

conditions of exposure to humans.

A. p-Toluidine

FDA has estimated the lifetime

exposure to p-toluidine from the

petitioned use of D&C Violet No. 2 in

glycolide/dioxanone/trimethylene

carbonate tripolymer absorbable sutures

to be no more than is 0.3 nanogram (ng)/

p/d (Ref. 2). The agency used data from

a long-term rodent bioassay on ptoluidine conducted by Weisburger et

al. (Ref. 1), to estimate the upper-bound

limit of lifetime human risk from

exposure to this chemical resulting from

the proposed use of the additive. The

authors reported that the rodent

bioassay showed that the test material

caused an increased incidence of

hepatomas (liver tumors).

Based on the agency’s estimate that

exposure to p-toluidine will not exceed

0.3 ng/p/d. FDA estimates that the

upper-bound limit of lifetime human

risk from the proposed use of the subject

additive is 2 x 10-11 or 2 in 100 billion

(Ref. 4). Because of the numerous

conservative assumptions used in

calculating the exposure estimate, the

actual lifetime-averaged individual

exposure to p-toluidine is likely to be

substantially less than the estimated

exposure, and therefore, the probable

lifetime human risk would be less than

the upper-bound limit of lifetime

human risk. Thus, the agency concludes

that there is reasonable certainty that no

harm from exposure to p-toluidine

would result from the proposed use of

the additive.

B. Specifications

The agency has also considered

whether specifications are necessary to

control the amount of p-toluidine

present as an impurity in D&C Violet

No. 2. The additive is currently

produced as a certified color additive

for use in externally applied drugs and

cosmetics, in sutures, and in contact

lenses in accordance with 21 CFR part

80. Based upon the low level of

exposure to p-toluidine that results

under the current specifications for D&C

Violet No. 2 in § 74.1602 (21 CFR

74.1602), the agency concludes that the

specifications listed in § 74.1602 are

adequate to ensure the safe use of this

color additive and to control the amount

of p-toluidine that may exist as an

impurity in the color additive when

used in glycolide/dioxanone/

trimethylene carbonate tripolymer

absorbable sutures for general surgery.

VII. Conclusions on Safety

FDA has evaluated the data and

information in the petition and other

relevant material. Based on this

information the agency concludes that:

(1) The proposed use of D&C Violet No.

2, at a level not to exceed 0.2 percent

by weight of the suture material, for

coloring glycolide/dioxanone/

trimethylene carbonate tripolymer

absorbable sutures is safe; and (2) the

color additive will achieve its intended

coloring effect, and thus, is suitable for

this use. The agency therefore, is

amending the color additive regulations

in § 74.3602 as set forth below.

VIII. Inspection of Documents

In accordance with § 71.15 (21 CFR

71.15), the petition and the documents

that FDA considered and relied upon in

reaching its decision to approve the

petition are available for inspection at

the Center for Food Safety and Applied

Nutrition (address above) by

appointment with the information

contact person listed above. As

provided in § 71.15, the agency will

delete from the documents any

materials that are not available for

public disclosure before making the

documents available for inspection.

IX. Environmental Impact

The agency has carefully considered

the potential environmental effects of

this action. FDA has concluded that the

action will not have a significant impact

on the human environment, and that an

environmental impact statement is not

required. The agency’s finding of no

significant impact and the evidence

supporting that finding, contained in an

environmental assessment, may be seen

in the Dockets Management Branch

(address above) between 9 a.m. and 4

p.m., Monday through Friday.

X. Objections

Any person who will be adversely

affected by this regulation may at any

time on or before May 26, 1998, file

with the Dockets Management Branch

(address above) written objections

thereto. Each objection shall be

separately numbered, and each

numbered objection shall specify with

particularity the provisions of the

regulation to which objection is made

and the grounds for the objection. Each

numbered objection on which a hearing

is requested shall specifically so state.

Failure to request a hearing for any

particular objection shall constitute a

waiver of the right to a hearing on that

objection. Each numbered objection for

which a hearing is requested shall

include a detailed description and

analysis of the specific factual

information intended to be presented in

support of the objection in the event

that a hearing is held. Failure to include

such a description and analysis for any

particular objection shall constitute a

waiver of the right to a hearing on the

objection. Three copies of all documents

shall be submitted and shall be

identified with the docket number

found in brackets in the heading of this

document. Any objections received in

response to the regulation may be seen

in the Dockets Management Branch

between 9 a.m. and 4 p.m., Monday

through Friday.

XI. References

The following references have been

placed on display in the Dockets

Management Branch (address above)

and may be seen by interested persons

between 9 a.m. and 4 p.m., Monday

through Friday.

1. Weisburger, E. K. et al., ‘‘Testing of

Twenty-One Environmental Aromatic

Amines or Derivatives for Long-Term

Toxicology or Carcinogenicity,’’ Journal of

Environmental Pathology and Toxicology,

2:325–356, 1978.

2. Memorandum from the Chemistry

Review Team, FDA, to the Indirect Additives

Team, FDA, concerning ‘‘CAP 5C0248:

United States Surgical Corporation. Use of

D&C Violet No. 2 as a colorant in synthetic

absorbable surgical suture. Correction of

Exposure Estimate.,’’ dated March 6, 1997.

3. Kokoski, C. J., ‘‘Regulatory Food

Additive Toxicology’’ in Chemical Safety

Regulation and Compliance, edited by F.

Homburger and J. K. Marquis, published by

S. Karger, New York, NY, pp. 24–33, 1985.

4. Report of the Quantitative Risk

Assessment Committee, FDA, concerning

‘‘Upper Bound Lifetime Risk for p-Toluidine

in D&C Violet No. 2 Used as a Color Additive

for glycolide/dioxanone/trimethylene

carbonate tripolymer absorbable sutures

designated as USSC Monofilament polysorb

sutures (UMPS),’’ dated September 4, 1997.

List of Subjects in 21 CFR Part 74

Color additives, Cosmetics, Drugs.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, 21 CFR part 74 is

amended as follows:

PART 74—LISTING OF COLOR

ADDITIVES SUBJECT TO

CERTIFICATION

1. The authority citation for 21 CFR

part 74 continues to read as follows:

Authority: 21 U.S.C. 321, 341, 342, 343,

348, 351, 352, 355, 361, 362, 371, 379e.

2. Section 74.3602 is amended by

adding paragraph (b)(2)(v) to read as

follows:

§ 74.3602 D&C Violet No. 2.

* * * * *
20098 Federal Register / Vol. 63, No. 78 /Thursday, April 23, 1998 /Rules and Regulations

(b) * * *

(2) * * *

(v) At a level not to exceed 0.2 percent

by weight of the suture material for

coloring glycolide/dioxanone/

trimethylene carbonate tripolymer

absorbable sutures for use in general

surgery.

* * * * *

Dated: April 16, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–10779 Filed 4–22–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF LABOR

Occupational Safety and Health

Administration

29 CFR Parts 1910 and 1926

[Docket No. H–049]

RIN 1218–AA05

Respiratory Protection; Correction

AGENCY: Occupational Safety and Health

Administration (OSHA), Department of

Labor.

ACTION: Final rule; correction.

SUMMARY: OSHA is correcting errors in

the regulatory text of the Respiratory

Protection final rule that appeared in

the Federal Register on January 8, 1998

(63 FR 1152).

DATES: These corrections become

effective on April 23, 1998.

FOR FURTHER INFORMATION CONTACT:

Bonnie Friedman, Director, OSHA

Office of Public Affairs, Room N–3647,

U.S. Department of Labor, 200

Constitution Avenue, N.W.,

Washington, D.C. 20210; Telephone:

(202) 219–8148.

SUPPLEMENTARY INFORMATION: On

January 8, 1998 (63 FR 1152), OSHA

promulgated revised regulations for

respiratory protection in general

industry (part 1910), shipyards (part

1915), marine terminals (part 1917),

longshoring (part 1918), and

construction (part 1926).

Subsequently, technical and

typographic errors were discovered in

the regulatory text. This notice is being

published to correct these errors. With

the exception of the explanations

discussed below, these corrections are

self-explanatory.

In paragraph (i)(1)(ii), Breathing air

quality and use, the reference to ‘‘Type

1—Grade D breathing air’’ has been

corrected to read ‘‘Grade D breathing

air’’ to conform to the ANSI/

Compressed Gas Association

Commodity Specification for Air, G–

7.1–1989.

Paragraph (n)(3) is corrected to state

that the respiratory protection

provisions of the previous standard, 29

CFR 1910.134 as contained in the 29

CFR parts 1900 to 1910.999 edition of

the Code of Federal Regulations

published July 1, 1997, will continue in

effect until October 5, 1998, the date for

full compliance with the revised

standard, rather than April 8, 1998, the

effective date of the revised standard.

In Appendix A, in the protocol for the

Bitrex qualitative fit test, the part

numbers for the fit test hood assembly

now match the part numbers given in

the saccharin qualitative fit test

protocol. Also, in the generated aerosol

quantitative fit testing protocol, a

reference for using P100 filters as one of

the methods to filter exhaust air flow

from the fit test chamber is incorrect

and is deleted. In the condensation

nuclei counter quantitative fit test

protocol, the requirement in paragraph

(a)(1) that a high-efficiency filter be

fitted has been revised to allow for the

fit testing of additional types of filters as

appropriate. For the controlled negative

fit test protocol, the pressure setting for

the default test pressure has been

changed from ¥1.5 mm to the correct

value of ¥15 mm.

In Appendix C a typographic error in

Part A, Section 2, question 11(e) has

been corrected to read ‘‘d. Any other eye

or vision problem: Yes/No’’.

Appendix D has been entitled

‘‘mandatory’’ since the employer is

required by paragraph (k)(6) of the

standard to provide the basic advisory

information on respirators presented in

Appendix D to any employees who

voluntarily use respirators.

Since some of the 13 carcinogens are

vapors, language has been added to

paragraph (c)(4)(iv) of § 1910.1013

permitting the use of air-purifying

canisters or cartridges, in addition to

particulate filters. This provision

requires appropriate respirator filters for

these carcinogens.

This correction removes the provision

in the revised Lead standard

(§ 1910.1025(f)(1)(i)) that limits

respirator use to a maximum of 4.4

hours per day. The 4.4 hour requirement

had been removed earlier by OSHA (see

60 FR 52859).

Typographic errors in provisions in

the Benzene standard (§ 1910.1028

(g)(2)(i)), Acrylonitrile standard

(§ 1910.1045 (h)(2)(i)), and the

Formaldehyde standard (§ 1910.1048

(g)(2)(i)) that referenced § 1910.134

(d)(3)(iii)(b)(1) have been corrected to

read (d)(3)(iii)(B)(1).

Appendix E of the

Methylenedianiline standard

(§ 1910.1050), which specifies fit testing

protocols, has been removed to match

changes made to other substance

specific standards. These changes

require the use of the fit testing

protocols in Appendix A of the revised

respiratory protection standard.

The Methylene chloride standard

limits respiratory protection to

supplied-air respirators except for

emergency escape. Paragraphs

(d)(3)(iii)(B) (1) and (2) of the revised

respiratory protection standard address

the use of end-of-service-life indicators

or change schedules for cartridges and

canisters, and do not apply to suppliedair or emergency escape respirators.

Accordingly, these paragraphs have

been removed from the respiratory

protection program required by the

Methylene chloride standard to be in

compliance with the revised § 1910.134

respiratory protection standard.

The correction to paragraph (h)(2)(iv)

of the Asbestos standard for the

construction industry reinstates an

earlier revision made by OSHA to this

standard. This revision permitted the

use of PAPRs with HEPA filters or

supplied-air respirators with HEPA

egress cartridges under the conditions

specified in this paragraph (see 60 FR

33985).

All these corrections to the standard

are deemed to be ‘‘minor’’ amendments

within the meaning of 29 CFR 1911.5.

OSHA finds good cause, pursuant to 29

CFR 1911.5 and the Administrative

Procedure Act, for promulgating the

corrections without notice and

opportunity for public comment.

Correction of Publication

The following corrections are made in

the final rule for Respiratory Protection

published in the Federal Register on

January 8, 1998 (63 FR 1152).

Respiratory Protection [Correction]

§ 1910.134 [Correction]

1. On page 1275, first column,

paragraph (i)(1)(ii), lines 2 and 3, are

corrected to read ‘‘meet at least the

requirements for Grade D breathing air

described in’’.

2. On page 1275, first column,

paragraph (i)(4)(ii), line 4, is corrected to

read ‘‘requirements for Grade D’’.

3. On page 1276, second column,

paragraph (n)(3), line 2, the date ‘‘April

8, 1998’’ is corrected to read ‘‘October

5, 1998’’.

4. On page 1278, third column,

paragraph (a)(1), line 10, the reference

‘‘parts #14 and #15’’ is corrected to read

‘‘parts # FT 14 and # FT 15’’.