Phenol, 4-(phenylamino)-, sulfurized, leuco deriv.

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06-20 December 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

phenol, 4-(phenylamino)-, sulfurised, leuco deriv.

Molecular formula:

not applicable

IUPAC Name:

phenol, 4-(phenylamino)-, sulfurised, leuco deriv.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (males: 281 - 307 grams; females: 191 - 204 grams).
- Housing: Individual housing in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle.

IN-LIFE DATES: From: 06 to 20 December 2012

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Dose volume: 2000 mg/kg (based on main component C.I. Leuco Sulphur Brown 96). This dose corresponded to 10200 mg test substance including C.I. Leuco Sulphur Brown 96, based on a correction factor of 5.1 (to correct for water content of the test substance).

DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor. Correction was made for
water content of the test substance (correction factor 5.1).

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.

Statistics:

None.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

Flat/hunched posture, piloerection, ptosis, uncoordinated movements, hypothermia and/or chromodacryorrhoea were noted among all animals on Days 1 and/or 2.

The treated skin area of all animals showed black staining on Days 2 and 3 and red staining between Days 4 and 15. Other findings that were noted on the treated skin area included swelling, focal erythema and scales between Days 2 and 5.

Body weight:

The changes noted in body weight gain were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Conclusions:

In an acute dermal toxicity study with rats, performed sccording to OECD 402 guidelines, an LD50 of >2000 mg/kg bw was determined.

Executive summary:

In an acute dermal toxicity study, the test substance was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred. Flat/hunched posture, piloerection, ptosis, uncoordinated movements, hypothermia and/or chromodacryorrhoea were noted among all animals on Days 1 and/or 2. The treated skin area of all animals showed black staining on Days 2 and 3 and red staining between Days 4 and 15. Other findings that were noted on the treated skin area included swelling, focal erythema and scales between Days 2 and 5.

The changes noted in body weight gain were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of C.I. Leuco Sulphur Brown 96 in Wistar rats was established to exceed 2000 mg/kg body weight.