Mequinol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 23 sept 2008 to 19 dec 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, carried out without any deviations to the guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: OECD No 423 Acute Oral Toxicity – Acute Toxic Class Method

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Mequinol

EC Number:

205-769-8

EC Name:

Mequinol

Cas Number:

150-76-5

Molecular formula:

C7H8O2

IUPAC Name:

4-methoxyphenol

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories Ltd
- Age at study initiation: 9 weeks for males and 11 weeks for females
- Weight at study initiation: 187.3 g - 263.0 g
- Fasting period before study: no fasting period
- Housing: individually in Makrolon type-3 cages with standard softwood bedding
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet
- Water (e.g. ad libitum): community tap water from Füllinsdorf
- Acclimation period: 7/8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): air-conditioned with 10-15 airs changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: 01 oct 2008 To: 15 oct 2008

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: purified water

Details on dermal exposure:

TEST SITE
- Area of exposure: back of animals, skin area of 12 cm2 and 9 cm2 in the males and females
- % coverage: approximately 10% of the total body surface
- Type of wrap if used: a surgical gauze patch


TEST MATERIAL
- Concentration: 2000 mg/kg bw
- Concentration used: yes
- For solids, paste formed: yes


VEHICLE
- Amount(s) applied: 0.1 mL

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: 15 days
- Frequency of observations: during the first 30 minutes, at approximately 1, 2, 3 and 5 hours after administration on test day 1 and twice daily for viability / Mortality and once daily for clinical signs during days 2-15
- Weighing : on test days 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight, macroscopic examination

Statistics:

no statistical analysis was used

Results and discussion

Preliminary study:

A single animal of each sex was treated first. Since no death as well as no severe local effects or severe systemic symptoms were observed after the 24-hour exposure, the test was completed using the four remaining male and female animals for an exposure period of 24-hours.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no deaths occured during the study

Clinical signs:

other: No clinical signs were observed in all 5 males and 5 females within the first 30 minutes following the treatment. No severe clinical signs were observed in all animals. Only slight signs were observed such as: - ruffled fur: in 4 males and 1 female at the

Gross pathology:

No macroscopic findings were recorded at necropsy.

Other findings:

Local dermal signs
Delayed local dermal reactions were observed in all males and females and consisted of erythema, oedema, scaling, focal to maculated crusts. The skin was affected from test day 3 to 5 (in most of the animals) to test day 7, 8, 11, 12 or up to the end of the observation (test day 15).

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD 50 (rat): greater than 2000 mg/kg body weight

Executive summary:

In an acute dermal toxicity study B96175, groups of 5 Wistar male and 5 Wistar female rats were dermally exposed to Paramethoxyphenol for 24 hours to 10% of the total body surface at dose of 2000 mg/kg bw.

Animals then were observed for 15 days.

Dermal LD₅₀ > 2000 mg/kg bw

Paramethoxyphenol is not classified based on the LD₅₀. (PMP is also not officially classified)

Slight clinical signs (sedation and ruffled fur) and local signs (erythema and scaling crusts) were generally observed in almost all animals. There were no treatment related macroscopic examination or changes in body weight.