1,3-bis(isocyanatomethyl)benzene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 25, 1992 - July 9, 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in accordance with OECD 402 and GLP. There is 1 deviation: during the 14 days observation period, the animals were not caged individually but by sex. But it is assumed that this deviation does not significantly influence the reliability of the study. Batch number and purity not given.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

; during the 14 days observation period, the animals were not caged individually but by sex

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,3-bis(isocyanatomethyl)benzene

EC Number:

222-852-4

EC Name:

1,3-bis(isocyanatomethyl)benzene

Cas Number:

3634-83-1

Molecular formula:

C10H8N2O2

IUPAC Name:

1,3-bis(isocyanatomethyl)benzene

Details on test material:

- Name of test material (as cited in study report): XDI: 1,3-Benzenebis(methylisocyanate)
- Appearance: clear colourless liquid
- Specific gravity (determined before the study): 1.188

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, UK
- Age at study initiation: approximately 10 to 14 weeks old
- Weight at study initiation:
Males: 244 - 265 g
Females: 202 - 243 g
- Fasting period before study: not applicable
- Housing:
The animals were housed in suspended polypropylene cages furnished with softwood sawdust. The animals were housed individually during the 24-hour exposure period and in groups of 5, by sex, for the remainder of the study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23 °C
- Humidity (%): 47 - 75% (on 2 occasions >70%)
- Air changes (per hr): 15 per hr
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: an area equivalent to 10% of the total body surface ( 5 cm x 4 cm)
- Type of wrap if used: surgical gauze semi-occluded with a piece of self-adhesive bandage (HYPERTIE), the bandage was further secured with a piece of BLENDERM wrapped around each end

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual material was removed by wiping with cotton wool moistened with arachis oil
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw = 1.69 mL/kg bw
- Concentration (if solution): undiluted

VEHICLE
Not applicable

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Deaths and overt signs of toxicity were recorded 0.5; 1; 2 and 4 hours after dosing and subsequently once daily for 14 days
Individual bodyweights were recorded prior to treatment on day 0 and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: dermal reactions were also recorded

Statistics:

Not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

other: - No signs of systemic toxicity were noted - Adverse skin reactions were noted at the treatment site of all animals from day 5 onwards These reactions included: *well-defined erythema and oedema *light brown discolouration *small superficial scattered sca

Gross pathology:

No abnormalities were noted

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study conducted in accordance with OECD 402 and GLP (limit test), an LD50 of >2000 mg/kg bw was found.

Executive summary:

In an acute dermal toxicity study, conducted in accordance with OECD 402 and GLP (limit test), 5 female and 5 male rats were semi-occlusively exposed for 24 hours to the undiluted test substance at a dose of 2000 mg/kg bw. No apparent systemic toxicity was seen and no deaths occurred. Dermal reactions were noted, starting from day 5 onwards. The conducted gross pathology did not detect any abnormalities.