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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1987-09-15 to 1987-09-29
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Non-GLP guideline study. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the hazardous degradation product (alcohol) released from the target substance. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance, which might change the hazardous properties of the target substance compared to the properties of the pure alcohol. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across data from the degradation product (relevant alcohol) to evaluate irritation, sensitization and the short term and long-term toxicological effects and mutagenicity of the target substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: clear liquid
- Analytical purity: 99.5%
- Lot/batch No.: production date 1987-08-20
- Storage condition of test material: dry under inert gas atmosphere

Test animals

Species:
rat
Strain:
other: WISW (SPF TNO)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation: 173.1 g (mean)
- Fasting period before study: no data
- Housing: Macrolon cages Type III, in groups of 1 to 5 animals
- Diet (e.g. ad libitum): R10 rat diet; Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): tap water
- Acclimation period: 4 to 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 °C
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12 hours


IN-LIFE DATES: From: day -1 To:day 14 after initiation

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: >10% of the body surface; clipped 24 h before initiation
- % coverage: >10
- Type of wrap if used: the test site was covered with a gauze patch (5x7cm) and fixed with a cotton wrap.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3.604 ml/ kg bw, i.e. 3000 mg/kg bw
- Concentration (if solution): neat

Duration of exposure:
24 hours
Doses:
3000 mg/kg bw
No. of animals per sex per dose:
5 per sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days -1, 1, 7, and 14 after initiation
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
The LD50 was calculated according to Litchfield and Wilcoxon (1949). Pharmacol. Exp. Ther. 96: 99

Results and discussion

Preliminary study:
There was no mortality neither in male nor female rats. The dermal LD50 was >3000 mg/kg body weight in rats.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Mortality:
There was no mortality neither in male nor female rats.
Clinical signs:
Animals were excited until 1 hour after test substance application, and free of symptoms thereafter.
Body weight:
Body weight development was not affected by the treatment compared to controls (contol data not reported). Mean body weights were as tabulated below. Mean body weight gain was 28.7 g within 14 days after treatment.


Day after initiation Mean body weight [g]
0 before treatment 173.1
1 171.4
7 186.5
14 201.8



Gross pathology:
Mucosa of the small intestine was hyperaemic in 2 animals; red coloured urine was noted in one rat, associated with changes in the kidney.

Any other information on results incl. tables

Body weight development in treated rats (combined males and females):

Day after initiation

Mean body weight [g]

0 before treatment

173.1

1

171.4

7

186.5

14

201.8

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 was >3000 mg/kg body weight in rats.
Executive summary:

The acute dermal toxicity of 2-ethylhexanol was tested in rats according to OECD 402. 5 animals of either sex were exposed to 3000 mg/kg bw for 24 hours under a semiocclusive dressing. There were no mortalities within the 14 days observation period. The body weight development was not affected, and there were no clear clinical signs or observations during necropsy which could be related to the treatment. Therefore, the dermal rat LD50 was >3000 mg/kg bw in this study (Hüls AG, 1987).