2-methoxy-4-propylphenol

Acute Toxicity: dermal

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

Test material information

Constituent 1

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:

other: - 2/5 females showed urogenital staining 4 h after dosing. No other clinical signs were observed.

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.