2-methylpropyl-(R)-2-hydroxypropanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

1994-06-16 to 1994-09-22

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. n-Propyl lactate used as read-across partner.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

, adopted February 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

53651-69-7

Cas Number:

53651-69-7

IUPAC Name:

53651-69-7

Constituent 2

Reference substance name:

n-propyl lactate

IUPAC Name:

n-propyl lactate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): n-Propyl-lactate
- Chemical name: (5)-2-hydroxypropanoic acid propylester
- Physical state: Clear, colourless liquid
- Analytical purity: 99.5 %
- Density: 1.004 kg/L
- Lot/batch No.: 3
- Storage condition of test material: ambient

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: 5-6 weeks
- Weight at study initiation: males: 358 to 402 g, female: 210 to 241 g
- Fasting period before study: No
- Housing: In stainless steel cages with wire-screen bottom and front, 5 animals per cage; during dermal exposure the animals were housed individually
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 65 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 52.5-92.5 (upper limit higher than the intended 70 %, because of meterological circumstances or because of wet cleaning of the animals room; the 92.5 % peak occured for ca one hour at most)
- Air changes (per hr): 10
- Photoperiod (hrs dark/hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 20cm²
- % coverage: 10 % of the total body surface
- Type of wrap if used: exposed area was covered by plastic foil, which was fixed by adhesive tape and the entire trunk of the rat was wrapped with an impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was rinsed with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg bw
- Concentration (if solution): 99.5 %
- Constant volume or concentration used: Yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observations: within 1 h and 4 h after the start of dosing, and subsequently at least once daily throughout an observation period
- Frequency of weighing: on day 0, 3, 7 and 14
- Necropsy of survivors performed: On day 14 of the study, all animals were killed with carbon dioxide and examined for external changes. Next the abdomen and the thorax of each animal was opened and examined for gross pathological changes.

Statistics:

N.A.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: Apart from encrustation of the nose on day 1 and day 3 no clinical symptoms were observed.

Gross pathology:

Macroscopic examination of the animals at the end of the observation period did not reveal any treatment-related gross alterations.

Other findings:

Dermal reactions:
After treatment with the test substance, only slight encrustation was observed in two males and one female on day 1 of the study.

Any other information on results incl. tables

Table 1: Acute dermal toxicity of n-propyl lactate in rats
Animal no.	Dose applied (mL)*	Body weights (g) recorded on day				Mortality -/+
		0	3	7	14
Males:
52	0.7	358	348	359	363	-
54	0.8	385	380	391	399	-
56	0.8	402	395	401	416	-
58	0.8	392	380	394	401	-
60	0.7	360	350	355	369	-
	mean	379	371	380	390
	sem**	9	9	10	10
Females:
51	0.4	215	212	219	225	-
53	0.5	227	222	219	224	-
55	0.4	210	218	218	221	-
57	0.5	241	233	236	249	-
59	0.4	217	203	205	209	-
	mean	222	218	219	226
	sem**	5	5	5	7

*= dose of 2 mL per kg body weight of the undiluted test substance

**= standard error of the mean

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, since no mortality occurred in an acute dermal toxicity study, the dermal LD 50 of n-propyl lactate is considered to exceed 2000 mg/kg bw, both in males and females

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402, groups of Wistar rats (5/sex) were dermally applied a dose of 2000 mg/kg bw of n-propyl lactate (99.5% purity).

The animals were observed for 14 days after the single exposure. No mortalities occured after treatment with the test substance at 2000 mg/kg bw. Therefore, the dermal LD₅₀ value is greater than 2000 mg/kg body weight, both in male and female rats. n-Propyl lactate is used as read-across partner to isobutyl-R-lactate.