9-Octadecenoic acid (Z)-, monoester with 1,2,3-propanetriol ester with boric acid (H3BO3)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 November 1982 to 30 November 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guidelines and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

9-Octadecenoic acid (Z)-, monoester with 1,2,3-propanetriol ester with boric acid (H3BO3)

EC Number:

264-092-6

EC Name:

9-Octadecenoic acid (Z)-, monoester with 1,2,3-propanetriol ester with boric acid (H3BO3)

Cas Number:

63310-16-7

Molecular formula:

C21H39O5B (based on the representative structure below)

IUPAC Name:

2-hydroxy-3-{[hydroxy({2-hydroxy-3-[(9Z)-octadec-9-enoyloxy]propoxy})boranyl]oxy}propyl (9Z)-octadec-9-enoate; 3-{[bis({2-hydroxy-3-[(9Z)-octadec-9-enoyloxy]propoxy})boranyl]oxy}-2-hydroxypropyl (9Z)-octadec-9-enoate; {2-hydroxy-3-[(9Z)-octadec-9-enoyloxy]propoxy}boronic acid

Test material form:

liquid: viscous

Details on test material:

- Physical state: liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Nitabell Rabbitry, Hayward, California, USA
- Age at study initiation: 10 - 12 weeks
- Weight at study initiation: 2.21 - 2.44 kg (males); 2.09 - 2.46 kg (females)
- Housing: individually in wire-bottom cages
- Diet: approximately 115 g Purina Rabbit Chow #5321, daily
- Water: ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 21 ºC
- Humidity (%): 55 - 77 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From 16 November 1982 to 30 November 1982

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- The fur on the trunks of the animals was clipped free of fur. On the day of testing, the exposed skin was abraded with a hypodermic needle
- Type of wrap if used: the test material was held in contact with the animals skin with a plastic sheet. Paper towels were wrapped over the plastic sheet to prevent tearing.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the mean volumes of test material administered were 12.0 mL (males) and 11.5 mL (females) The mean weights of the test material administered were 12.0 g (males) and 11.5 g (females)

Duration of exposure:

24 hours

Doses:

0 (controls), 5.0 g/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed frequently on the day of dosing and at least once each morning and late afternoon on each subsequent day (except at weekends when observations were made once daily). Bodyweights were recorded prior to dosing and on 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: animals were examined for gross pathological changes. The following organs and tissues were examined: skin, spleen, pancreas, stomach, small and large intestine, liver, adrenals, kidneys, gonads, uterus or seminal vesicles, bladder, heart, thymus, salivary glands, lungs, trachea, thyroid and fat.
- Histopathology: sections of skin from each animal and any other abnormal appearing tissue were submitted for histopathological examination

Statistics:

The weights of the treated animals were compared to the control animals using Student's t-test.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study.

Clinical signs:

other: Reduced food intake was observed in both treated and control animals.

Gross pathology:

At necropsy, dry and flakey skin was observed in several treated animals. No other signs of toxicity or gross pathological changes attributable to treatment with the test material were observed.

Other findings:

Histopathological examination of treated skin sections revealed diffuse hyperkeratosis in seven of the ten treated animals. The changes seen in the skin were reported to be easily reversible.

Any other information on results incl. tables

Table 1: Mean (± s.d) bodyweights (kg)

Group	Pre-test	7 days	14 days
Control males	2.33 (0.11)	2.45 (0.13)	2.62 (0.08)
Treated males	2.30 (0.07)	2.35 (0.10)	2.50* (0.06)
Control females	2.23 (0.15)	2.20 (0.15)	2.44 (0.07)
Treated females	2.22 (0.09)	2.17 (0.12)	2.37 (0.16)

* = significantly different from control (p ≤ 0.05)

Table 2: Individual Skin Reactions of Treated Animals

Animal no.	Tissue	Pathological observation
24M	skin	diffuse hyperkeratosis; multifocal non-suppurative dermatitis
56M	skin	no significant change
70M	skin	diffuse hyperkeratosis-2
98M	skin	no significant change
188M	skin	diffuse hyperkeratosis-1
61F	skin	diffuse hyperkeratosis-1
	liver	diffuse chronic cholangitis-2
64F	skin	diffuse hyperkeratosis-2
68F	skin	no significant change
126F	skin	diffuse hyperkeratosis-1
133F	skin	diffuse hyperkeratosis-1

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute dermal LD50 of the test material was estimated to be in excess of 5000 mg/kg to male and female rabbits. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.

Executive summary:

The dermal toxicity of the test material was determined following a methodology equivalent to that in standardised guidelines OECD 402 and EU Method B.3. During the study, five male and female rabbits received a single dermal application of 5000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. An additional group of 5 males and 5 females served as the controls. Under the conditions of the study none of the animals died and no signs of toxicity attributable to treatment with the test material were observed. The mean bodyweight of treated male animals was significantly less than that of the controls at 14 days after dosing. At necropsy, some treated animals showed dry and flakey skin but no other gross pathological changes which could be related to treatment with the test material were observed. Histopathological evaluation of treated skin sections revealed mild diffuse hyperkeratosis which was easily reversible. No permanent alterations in the structure of the skin would be anticipated in these animals. The acute dermal LD50 of the test material was subsequently estimated to be in excess of 5000 mg/kg to male and female rabbits.