Distillation residue, butyl alcohols production, rectification

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

1992-03-06

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Repeated-dose dermal toxicity, similar to that of OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test), studies performed with the only identified and quantified constituent of the registered substance, 2-ethylhexanol. Studies performed with pregnant Fischer F344 rats and they study the developmental toxicity of 2-ethylhexanol. In the absence of the registered substance these studies serve as a good surrogate studies: a) it represents the effects of the only identified and quantified constituent of the substance, since the constituents of this registered UVCB-substance cannot be quantified and its composition varies to the degree that composition cannot be fixed. b) studies have been performed with good quality and data is published in a peer-reviewed journal. c) they provide adequate information on effect levels of 2-ethylhexanol when administered via dermal route.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD TG422: dermal route

Deviations:

yes

Principles of method if other than guideline:

Pregnant Fischer 344 rats were studied in two studies with an occluded dermal application:
1. Range-finding study
2. Main study

GLP compliance:

yes

Remarks:

U.S EPA Health effects guidelines and Good Laboratory Practice regulations.

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexan-1-ol

EC Number:

203-234-3

EC Name:

2-ethylhexan-1-ol

Cas Number:

104-76-7

Molecular formula:

C8H18O

Details on test material:

Surrogate material: 2-ethylhexanol.
Test substance - 2-ethylhexanol: 99,72% purity, gas chromatographic verification by the contract laboratory. (sample provided by the Shell developmental company, Houston, TX, USA). Gas chromatographic: at the beginning of the studies and in the end of the studies. Test material was verified to be stable over the treatment periods.

Control substances: 2-methoxyethanol (dermal reference) and valproic acid (cavage reference) had purities of 99,9% and 98,0%, respectively.

Test animals

Species:

rat

Strain:

Fischer 344

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Virgin F344 rats (CDF(R) F344 Crl./Br.)
- Source: Charles River Breeding Laboratories (Kingston, NY)
- Age at study initiation: 70 days / 63 days
- Weight at study initiation: males 175-200g / females 130-150g
- Gestational day 0: appearance of copulatory plug
- Housing: singly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2-week quarantine period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 42-65
- Air changes (per hr): not disclosed
- Photoperiod (hrs dark / hrs light): 12 hour

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: positive control for adverse effects on reproduction: 2-methoxyethanol

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
1.Rangefinding study: 0.5, 1, 2, 3 (ml/kg/day) equivalent to 420, 840, 1680, 2520 (mg/kg/day). Positive control: 2-methoxyethanol: 0.5 and 1.5 (ml/kg/day) equivalent to 420 and 1260 (mg/kg/day). Oral cavage reference compound: Valproic acid 400 mg/kg bw/day.
2. Main study: 0.3, 1, 3 (ml/kg/day) equivalent to 252, 840, 2520 (mg/kg/day).Positive control: 2-methoxyethanol 1 (ml/kg/day) equivalent to 840 (mg/kg/day)
- Concentration (if solution): 100%
- Constant volume or concentration used: no


VEHICLE
- No vehicle

Duration of treatment / exposure:

6-hours day

Observation period:

Before and after treatment

Number of animals:

Range-finding study: 8 animals per group
Main study: 25 animals per group

Details on study design:

TEST SITE
- Area of exposure: clipped and shaved dorsal skin of 9,7 cm2 (in the report ca. 1,5 cupic inches)
- Type of wrap if used:2 cupic inch gauze square, occluded with a Lycra-Spandex with Velcro closures. A 1.5x2.5 in. polyethylene patch was attached at the application site under the jacket.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped gently with moist gauze and blotted dry.
- Time after start of exposure: 6-hours


SCORING SYSTEM:
Draize score, FHSA (1987)

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

Draize score

Time point:

other: before and after 6-hour treatment

Score:

< 1.1

Max. score:

1.1

Reversibility:

fully reversible within: 18 hours

Remarks on result:

other: effects occurred during treatment and were transient or ameliorated after treatment ceased

Irritant / corrosive response data:

DERMAL IRRITATION
Treatment -related effects attributable to 2-ethylhexanol at the application site were exfoliation, encrustation and erythema. There was no edema. Exfoliation and encrustation occurred in both range-finding and main studies at all treatment levels of 2-ethylhexanol. There was no erythema or edema in sham controls. Erythema occurred during treatment with 2-ethylhexanol at levels of 830 mg/kg bw/day and above. Draize scores revealed that irritation was essentially mild. Maximum mean treatment scores occurred on gd10 at 1680 mg/kg bw/day (draize-score 0.4, range-finding study), on gd 11 at 2520 mg/kg bw/day (draize-score 1.1, range-finding study), and on gd 14 at 1680 mg/kg bw/day (draize-score 0.3, main study).

There was no exacerbation by continuent treatment. Erythema subsided immediately after cessation of treatment. There was no exfoliation, encrustation, erythema or edema at the application of control, 2-methoxyethanol.

Nasal encrustation and ocula encrustation and discharge were seen mostly in the main study with 2-ethylhexanol and 2-methoxyethanol and in sham controls. Since these effects occurred in controls and mostly disappeared after treatment ceased they are attributed to handling stress.

Other effects:

Weight reduction at highest concentrations (1680 and 2520 mg/kg bw/day).

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Repeated dermal exposure of 2-ethylhexanol lead with high doses (1680 and 2520 mg/kg bw/day) to slight reduction in body weight, otherwise it did not indicate properties which would lead to a concern for toxicity via dermal route. There was no exacerbation by continuent treatment. Erythema subsided after cessation of treatment. The only effect was mild skin irritation.