3-iodo-2-propynyl butylcarbamate

Endpoint summary

Description of key information

No positive skin reactions were seen following challenge with the test item in a guinea pig maximization test from 1993. However, the test item is legally classified as skin sensitizer Cat 1 according to Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation).

Consequently, in contrast to the study results the substance is classified as skin sensitizer Cat 1.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-08-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was conducted in 1993 when the GPMT was an internationally accepted and recommendet method.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: P 9303-7021

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature; in the dark

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Mollegaard Breeding Centre Ltd, Ejby, DK-4623 Lille Skensved
- Females nulliparous and non-pregnant: not specified
- Microbiological status of animals, when known: SPF
- Age at study initiation: adult
- Weight at study initiation: 233 - 306 g
- Housing: The guinea pigs were housed in opaque PPL (Type IV) cages, two or three to a cage
- Diet: ad libitum
- Water: ad libitum
- Indication of any skin lesions: none

ENVIRONMENTAL CONDITIONS
- Temperature: 21 +/- 3 °C
- Humidity: 55 +/- 15 %
- Air changes: 10 per hr
- Photoperiod: 6 a. m. to 6 p. m. light

Route:

intradermal

Vehicle:

paraffin oil

Concentration / amount:

0.08 % (w/w)

Day(s)/duration:

day 0

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

3.12 % (w/w)

Day(s)/duration:

day7 / 48 h

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

0.32 %

Day(s)/duration:

day 21 / 24 h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Neg control: 10
Positive control: 10
Test item: 20

Details on study design:

RANGE FINDING TESTS:
- investigation of intradermal irritancy of the test article
- investigation of topical irritancy of the test article
- investigation of topical irritancy of the test article on the flank of the animals using closed patch tests as in the main study

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal; 1 epicutaneous
- Exposure period: single injection and 48 h
- Test groups: 1
- Control group: negative control and positive control
- Site: dorsal skin and flank
- Frequency of applications: single applications
- Concentrations: 0.08 % (w/w) amd 3.12 % (w/w)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 21
- Exposure period: 24 h
- Test groups: 1
- Control group: negative control and positive control
- Site: flank
- Concentrations: 0.32 %
- Evaluation (hr after challenge): 24, 48, 72

Positive control substance(s):

yes

Remarks:

Dinitrochlorbenzene (DNCB)

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

9

Clinical observations:

No positive skin responses were observed in 9 animals.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.1 %

No. with + reactions:

9

Total no. in group:

9

Clinical observations:

Positive skin reaction were seen in 9 out of 9 animals.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.32 %

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No positive skin reactions were observed in 20 animals.

Table 1 Results of Magnusson Kligman Maximisation method

	time	application	Observations/Remarks
Induction 1	day 0	intradermal	irritation
Induction 2	day 7	topical	no skin reactions
Challenge	day 21	topical
Scoring 1	24 hours after challenge application		no skin reactions
Scoring 2	48 hours after challenge application		no skin reactions
Scoring 3	72 hours after challenge application		no skin reactions

Interpretation of results:

GHS criteria not met

Conclusions:

No positive skin reactions were seen following challenge with the test item. Hence, it is concluded that the test article did not produce a delayed contact hypersensitivity in guinea pigs.

Executive summary:

The allergenic potential of the test item was investigated according to one of the methods recommended in the OECD Guidelines No. 406, "Skin Sensitization", 1992. The delayed contact hypersensitivity test used was the Guinea Pig Maximization Test described by B. Magnusson and A.M. Kligman.

Forty animals divided into a positive control and a negative control group each with 10 animals and a test group with 20 animals were included in the study. The study comprised an induction and a sensitization (challenge) phase. The induction procedure consisted of intradermal injections and a closed patch topical application of the test article, positive control article (l-chlor-2,4-dinitorbenzol) or vehicle (paraffin oil and petrolatum) on the back of the guinea pigs, one week apart. The challenge procedure consisted of a closed patch topical treatment on the flank 3 weeks after the intradermal induction.The following concentrations were used for the induction and challenge phase.

	Test article	Pos. control article
Intradermal induction	0.08 % (w/w)	0.1 % (w/w)
Dermal induction	3.12 % (w/w)	1.0 % (w/w)
Challenge exposure	0.32 % (w/w)	0.1 % (w/w)

 

The skin reactions were evaluated 24, 48 and 72 hours after the challenge application. No positive skin reactions were observed after challenge in the test group.

Hence, it is concluded that the test article did not produce a delayed contact hypersensitivity in guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization in vivo I

The allergenic potential of the test item was investigated according to one of the methods recommended in the OECD Guidelines No. 406, "Skin Sensitization", 1992.The delayed contact hypersensitivity test used was the Guinea Pig Maximization Test described by B. Magnusson and A.M. Kligman.

Forty animals divided into a positive control and a negative control group each with 10 animals and a test group with 20 animals were included in the study. The study comprised an induction and a sensitization (challenge) phase. The induction procedure consisted of intradermal injections and a closed patch topical application of the test article, positive control article (l-chlor-2,4-dinitorbenzol) or vehicle (paraffin oil and petrolatum) on the back of the guinea pigs, one week apart. The challenge procedure consisted of a closed patch topical treatment on the flank 3 weeks after the intradermal induction.The following concentrations were used for the induction and challenge phase.

	Test article	Pos. control article
Intradermal induction	0.08 % (w/w)	0.1 % (w/w)
Dermal induction	3.12 % (w/w)	1.0 % (w/w)
Challenge exposure	0.32 % (w/w)	0.1 % (w/w)

 

The skin reactions were evaluated 24, 48 and 72 hours after the challenge application.No positive skin reactions were observed after challenge in the test group.

Hence, it is concluded that the test article did not produce a delayed contact hypersensitivity in guinea pigs.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin sensitization, the test item does not fulfill the criteria to be classified as skin sensitizer. However, the substance is legally classified as skin sensitizer Cat 1 (H317: "May cause an allergic skin reaction") according to Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation).