Benzene, 1-chloro-2,3-dimethyl-

Endpoint summary

Description of key information

3-Chloro-o-xylene was a skin sensitiser in a Kligman Maximisation Test according to OECD 406.

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:

From 25 Nov 2003 to 20 Dec 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

July 1992

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Reliable maximisation test

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Elm Hill Breeding Labs, Inc., Chelmsford, MA, USA
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: at least 21 days
- Weight at study initiation: 272.1 - 486.9 g
- Housing: in groups
- Diet: TEK Hi-Fiber Guinea Pig Diet 2041, Harlan Teklad, Madison, WI, USA, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal

Vehicle:

cotton seed oil

Concentration / amount:

50 %

Day(s)/duration:

single exposure

Adequacy of induction:

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

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100 %

Day(s)/duration:

Day 7

Adequacy of induction:

highest technically applicable concentration used

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100 %

Day(s)/duration:

Day 21

Adequacy of challenge:

other: highest concentration technically achievable

No. of animals per dose:

10 of each sex (test substance), 5 of each sex (negative control), 2 males and 3 females (positive control)

Details on study design:

RANGE FINDING TESTS: primary irritation study with 100%, 50%, 10%, and 1% diluted in cottonseed oil (CSO) for intradermal exposure and 100%, 75%, 50% and 25% in CSO for topical application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and topical)
- Exposure period: 48 h
- Test groups: Injection pair 1: 0.1 mL FCA 1:1 with CSO; Injection pair 2: 0.1 mL test substance; Injection pair 3: 0.1 mL test substance 1:1 with FCA: topical: pure test substance, occlusive covering
- Control group: Injection pair 1: 0.1 mL FCA 1:1 CSO; Injection pair 2: 0.1 mL CSO; Injection pair 3: 0.1 mL of 50% formulation of vehicle, 1:1 with FCA
- Site: Three pairs of intradermal injections were made so that on each side of the midline there was one row of three injections each. Injection pairs 1 and 2 were given in close proximity to each other cranially, whereas injection pair 3 was located caudally. The injection sites (6) were just within the boundaries of 2 x 4 cm; Topical: The test substance was spread over a 2 x 4 cm piece of filter paper to saturation or in a thick even layer. The patch was covered by an impermeable sheet and secured with a non-adhesive bandage, which was wound around the torso of the animal The dressing was left in place for 48 hours.
- Frequency of applications: twice
- Duration: 7 days
- Concentrations:

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: up to observation
- Test groups: Pieces of filter paper measuring 2 x 2 cm were secured to the flanks for 24 hours, with the same occlusive bandage as for topical induction, for the test and negative control animals: (1) on the left side, a patch was saturated with the test substance in the highest non-irritant concentration and (2) on the right side, a patch with the vehicle alone. In the positive control animals, the patch on the left side was saturated with 0.1% Benzocaine in ethanol instead of the test substance.
- Control group: see above
- Site: flanks
- Concentration: 100 %
- Evaluation (hr after challenge): 3 and 24 h

Positive control substance(s):

yes

Remarks:

0.1 % benzocaine in ethanol

Positive control results:

100 % erythema, extremely sensitising

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

16

Total no. in group:

20

Clinical observations:

16/20 the test animals (80% sensitisation) exhibited discrete to moderate erythema at the challenge exposure.Eight of the sixteen were still exhibiting signs of erythema at 48 hours after challenge. No systemic signs of toxicity were observed.

Remarks on result:

other: results at 3 and 24 h after challenge are combined

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

-

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no

Remarks on result:

other: results at 3 and 24 h after challenge are combined

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.1 %

No. with + reactions:

5

Total no. in group:

5

Clinical observations:

The positive control animals exhibited skin reactions at each observation point

Remarks on result:

other: results at 3 and 24 h after challenge are combined

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Under the conditions of this study, the test substance was strongly sensitising.

Executive summary:

1-Chloro-2,3-dimethylbenzene was tested in a skin sensitisation Kligman Maximisation Test (OECD 406) with guinea pigs. Based on a pretest, intradermal induction was performed with 50 % test item in cottonseed oil, topical induction with 100 %. The test item produced discrete to moderate erythema after challenge in sixteen out of twenty of the test animals (80 % sensitisation), and was therefore considered to be a strong sensitizer.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

1-Chloro-2,3-dimethylbenzene was tested in a skin sensitisation Kligman Maximisation Test (OECD 406) with guinea pigs. Based on a pretest, intradermal induction was performed with 50 % test item in cottonseed oil, topical induction with 100 %. The test item produced discrete to moderate erythema after challenge in sixteen out of twenty of the test animals (80 % sensitisation), and was therefore considered to be a strong sensitizer. As intradermal induction was performed with > 1% (50 %) test item, and resulted in a response > 60 % (80 %) a classification in Cat 1 B is required according to Regulation (EC) No 1272/2008, 3.4.2.2.3.3.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Due to the positive findings in a reliable in vivo skin sensitisation test a classification for sensitisation (1B) is required according to the criteria of Regulation (EC) No 1272/2008.