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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From June 10 to July 08, 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methoxy-4-propylphenol
EC Number:
220-499-0
EC Name:
2-methoxy-4-propylphenol
Cas Number:
2785-87-7
Molecular formula:
C10H14O2
IUPAC Name:
2-methoxy-4-propylphenol
Test material form:
liquid
Details on test material:
- Physical state: Colourless liquid
- Storage condition of test material: Stored at approximately 4 °C in the dark.

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent
- Weight at study initiation: 200-300 g
- Housing: Animals were individually housed in grid bottomed cages suspended over cardboard lined excreta trays.
- Diet: Pelleted rodent diet (SQC Rat and Mouse Maintenance Diet No. 1 Expanded, produced by Special Diets Services, Witham, Essex), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-24 °C
- Humidity: 47-66 %
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: June 10, 1992 To: July 08, 1992

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back area
- Type of wrap if used: A pad of surgical gauze 4 plies thick was placed on treated area and semi-occluded with an 'Elastoplast' elastic adhesive bandage (0.5 cm wide).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Dressings were removed and treated skin was washed by gentle swabbing with cotton wool soaked in warm water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
Duration of exposure:
24 h
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:
Animals were observed for mortality and clinical signs shortly after dosing and approximately 30 minutes, 1, 2 and 4 h after dosing and daily thereafter for 14 days. Individual body weights were recorded on Days 1, 8 and 15.
- Necropsy of survivors performed: Yes; after the 14 days observation period, all animals were killed by carbon dioxide asphyxiation and subjected to gross necropsy.
Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- No mortality was observed.
Clinical signs:
- 2/5 females showed urogenital staining 4 h after dosing. No other clinical signs were observed.
Body weight:
- Body weights were increased in males. Body weight changes in females were normal.
Gross pathology:
- One male showed minimal dilation of right kidney pelvis and one female showed moderate dilation of both kidney pelvises. No significant abnormalities were noted at necropsy.
Other findings:
None

Any other information on results incl. tables

Range-finding study:

- No mortality or clinical signs were observed at any dose level over 7 days study period.

Table 7.2.3/1: Individual bodyweights and bodyweight changes

Dose level

(mg/kg bw)

Animal number

and sex

Body weight (g)

at Day

Change in body weight

Day 1-15

1

8

15

2000

61 Male

253

297

351

98

62 Male

255

311

390

135

63 Male

259

299

362

103

64 Male

260

308

366

106

65 Male

246

291

353

107

Mean ± S.D

255 ± 5.6

301 ± 8.2

364 ± 15.6

110 ± 14.5

66 Female

221

230

247

26

67 Female

232

234

255

23

68 Female

234

247

269

35

69 Female

220

227

249

29

70 Female

212

226

238

26

Mean ± S.D

224 ± 9.1

233 ± 8.5

252 ± 11.5

28 ± 4.5

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the available information, the substance is:
- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw
- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).
Executive summary:

In an acute dermal toxicity study (limit test) performed similarly to OECD Guideline No. 402 and in compliance with GLP, a group of Crl:CD(SD)BR strain (VAF plus) rats (5/sex) was given a single dermal application of the undiluted test material at 2000 mg/kg bw to the clipped back area. Test sites were covered with a semi-occlusive dressing for 24 h. Animals were observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study all animals were sacrificed for macroscopic examination. Range finding study was conducted at the dose levels of 400, 1000 and 2000 mg/kg bw (1 rat/sex/dose) to determine the dose levels for the main study.

In the range-finding study, no mortality or clinical signs were observed at any dose level. In the main study, no mortality or clinical signs were observed except 2/5 females showed urogenital staining 4 h after dosing. No significant abnormalities were noted at necropsy.

Dermal LD50 Combined > 2000 mg/kg bw

Based on the available information, the substance is:

- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.