Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10SEP1981 - 19OCT1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed equivalent to OECD guidance. Study performed with substance analogue (maximum Klimisch score = 2).The rationale to read across these data is attached in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The test item was held on the skin with an impermeable covering. This can be considered worst case.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): H6XDI (Takenate 600; 1,3-bis(isocyanato-methyl)cyclohexane)
- Physical state: liquid (suspension in corn oil at 20% w/v)
- Storage condition of test material: at ambient temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent England
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 191 - 234g
- Housing: Individuall, in metal cages with wire mesh floors
- Diet: ad libitum, standard rodent diet (Laboratory Diet No. 1, Spratt's Limited, Barking, Essex, England)
- Water: ad libitum
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5±2.5
- Humidity (%): 31-57
- Air changes (per hr): Appr. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 10SEP1981 To: 19OCT1981

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: as supplied (main study) or as 20% suspension in corn oil (preliminary study)
Details on dermal exposure:
TEST SITE
- area of exposure: appr. 10% of total body surface
- % coverage: 100% of test site
- Type of wrap if used: Application site was covered with aluminium foil which was held in place with impermeable dressing encircled firmly around the trunk (occlusive coverage)

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with warm water (40-50°C), blotted dry with absorbent paper
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied (volume or weight with unit): maximum volume = 4.54 mL/ kg bw (density = 1.101 g/mL).
- Constant volume or concentration used: no
Duration of exposure:
24 hours
Doses:
0.1 and 0.5 mg/kg bw (preliminary study);
0.5, 2.0 and 5.0 g/kg bw (main study).
No. of animals per sex per dose:
2 (preliminary study);
5 (main study)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 5 days (preliminary study) and 14 days (main study)
- Frequency of observations: on day 1 regular observations, at least once daily in following period (animals observed for clinical signs and skin effects)
- Frequency of weighing: day 1, 8 and 15
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
No mortality occurred in the preliminary study.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in the main study.
Clinical signs:
Hunched posture and abnormal gait (waddling) were noted for treated animals (resolved by day 5).
Body weight:
Depressed body weight gains compared to controls were seen for treated males in the first week, and for treated females in second week of observation.
Gross pathology:
Terminal autopsy revealed congestion of the subcutaneous blood vessels under the site of application in one treated male and three treated females.
Other findings:
Slight or well-defined oedema, accompanied by dryness and sloughing of the epidermis was observed in all test substance treated animals on second day after removal. A gradual increase in severity of the reactions was observed and "in depth" skin damage was observed in four rats by day 10 and in three further rats by day 12. Well-defined to moderate erythema accompanied by well-defined oedema was seen in the remaining animals.
At termination, "in depth" damage persisted in two animals. Dryness and sloughing of the epidermis, with or without scab formation, was observed in nine treated animals on day 15.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
An acute dermal toxicity study was performed with 1,3-H6XDI. Since no mortality occurred at 5000 mg/kg bw, the LD50 of 1,3-H6XDI can be expected to exceed 5000 mg/kg bw.
Executive summary:

An acute dermal toxicity study was performed comparable to OECD with male and female rats. The test was performed with 1,3-H6XDI. No mortality occurred at 5000 mg/kg bw. Hunched posture and abnormal gait (waddling) were noted for treated animals (resolved by day 5). Depressed body weight gains compared to controls were seen for treated males in the first week, and for treated females in the second week of observation. Slight or well-defined oedema, accompanied by dryness and sloughing of the epidermis was observed in all test substance treated animals on the second day after removal. A gradual increase in severity of the reactions was observed and "in depth" skin damage was observed in four rats by day 10 and in three further rats by day 12. Well-defined to moderate erythema accompanied by well-defined oedema was seen in the remaining animals. Skin effects were also seen at autopsy: one treated male and three treated females were found to have congestion of the subcutaneous blood vessels under the site of application. Based on these data, the LD50 of 1,3-H6XDI can be expected to exceed 5000 mg/kg bw.