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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Draize, J.H. et al. 1965
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: powder or cake
Details on test material:
- Name of test material (as cited in study report): 2,4,6-Trimethyl phenol (TMP, Mesitol)
- Batch #: (Grade 8093)
- Description: White crystalline powder or cake
- Physical state: Solid
- Stability: Stability under normal storage and use conditions
- Storage: Room temperature (in hood preferably)
- Color: White

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: at least 12 weeks old (adult)
- Weight at study initiation: 2.02 – 2.26 kg
- Housing: Individual housing (Suspended stainless-steel cages); Bedding: Prochip, Harlan Teklad, Madison, WI (non-contact)
- Diet: TEK 8630 Rabbit Diet, Harlan Teklad, Madison, WI, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: minimum of 5 days, under the same conditions as for the actual test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12-Hour light/dark cycle, full spectrum fluorescent lights

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Remarks:
moistened
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- % coverage: 10
- Type of wrap if used: gauze patches two single layers thick, secured by wrapping the entire trunk of the animal with an impervious bandaging. Test sites were secured to prevent the animals from ingesting the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing: the skin was rinsed with USP Water for Injection
- Time after start of exposure: 24 hours

TEST MATERIAL
- TMP was moistened with water to a paste and applied.
Duration of exposure:
24 hours
Doses:
2000 mg/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 and weighing: The animals were observed frequently during the first day and then a careful clinical examination was made at least once a day. Animals were weighted at Day 0 (prior to dose administration), Day 7, and on Day 14 after euthanization.
- Necropsy of survivors performed: yes
- Other examinations performed: signs of erythema and edema after the exposure period according to the Draize Scale for Scoring Skin Reactions.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died during the course of the study.
Clinical signs:
No overt signs of systemic toxicity were evident during the course of the study.
Body weight:
All animals gained weight during the post-treatment period.
Gross pathology:
There were no abnormalities or lesions noted during necropsy.
Other findings:
SKIN REACTIONS
After removal of the TMP, necrosis was observed in six out of ten animals. The necrotic areas remained visible for the duration of the study. Slight to moderate erythema and edema was observed in the remaining four animals. All signs of erythema and edema were resolved by Day 11 of the study.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test, the LD50 was determined to be above 2000 mg/kg bw .
Executive summary:

In a GLP compliant OECD 402 guideline study, five New Zealand White rabbits per sex received a single topical application of 2000 mg/kg bw 2,4,6-Trimethyl Phenol (TMP, Mesitol) for 24 hours under occlusive conditions. After an observation period of 14 days animals were necropsied. Necrosis was observed in six out of ten animals after removal of the test substance. The necrotic areas remained visible for the duration of the study. No mortality was observed and no abnormalities or lesions were noted during necropsy. The LD50 was determined to be above 2000 mg/kg bw.