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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 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
other: OECD No 423 Acute Oral Toxicity – Acute Toxic Class Method
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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:
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 2-hour observation and persisted up to the 5-hour observation, test day 2, 4 or 5. The remaining male and females were observed with the same clinical signs and same severity at the 5-hour observation and persisted in one female on test day 2.
- sedation: in all males and females and was distributed from the 2-hour post-dose to test day 6.
- closed eyes: all animals, except two males, were observed with complete to almost complete closed eyes in the first hours following the treatment.
One female was more affected than the other males and females with addition clinical signs such a slightly poor coordination from the 2- to 5-hour post dose and vocalisation when touched from test day 3 to 5.
Body weight:
Two females lost slightly body weight (0.3% and 5.8%) during the first week after treatment and recovered until the end of the study.
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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.