Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: CD(SD)BR VAF/PlusT
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 7 weeks, females 8 weeks
- Weight at study initiation: males 200-253 g, females 197-222 g
- Housing: individually in stainless-steel mesh cages
- Diet: Agway Prolab Animal diet (RMH 3000) certified pellets, ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (° C): 21-22
- Humidity (%): 59-66
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 04 May 1993 To: 09 June 1993

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: an area of the dorsal skin
- Type of wrap if used: a fiber pad and an occlusive wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): running water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: the test material was administered as a solid moistened thoroughly with water
Duration of exposure:
24 hours
Doses:
2000 mg TMT 55/kg bw (equivalent to 1100 mg anhydrous TMT/kg bw)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (mortality, clinical signs, irritation using Draize scale): at day 0 and once daily thereafter (a total of 14 calendar days)
- Frequency of weighing: day 0 (prior to dosing), day 7 and day 14
- Necropsy of survivors performed: all animals were necropsied at the completion of the 14-day observation period

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: hydrated form TMT 55
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 100 mg/kg bw
Based on:
other: anhydrous form
Remarks on result:
other: recalculated value for anhydrous TMT based on 55% TMT
Mortality:
All animals survived to the end of the study.
Clinical signs:
Skin irritation was observed ranging from barely perceptible signs of irritation (slight erythema), to signs of strong irritation (servere erythema, slight edema) with irreversible skin damage. At the end of the observation period, scars were present at the application site for one of five males and all five females. In one female, a reduced amount of feces was noted on day 3. No other abnormal clinical signs were evident at any time during the 14-day observation period.
Body weight:
No effect on body weight observed. All animals gained weight normally.
Gross pathology:
A large spleen, noted for a single male, was processed for microscopic examination. Histologically, the increased size of the spleen was associated with hyperplastic lymphoid follicles. The cause for this change was not identified, but may have been related to the inflammatory response associated with the skin damage seen in this rat. No other treatment-related changes or signs of organ toxicity were evident at necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: not classified for hydrated form TMT 55; inconclusive for anhydrous TMT
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
In this acute dermal toxicity study in the rat the LD50 for the test item TMT 55 was greater than 2000 mg/kg bw (corresponding to > 1100 mg anhydrous TMT/kg bw) for both sexes.