Propanoic acid, 2-hydroxy-, ammonium salt (1:1), (2S)-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-03-10 to 2005-07-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Propanoic acid, 2-hydroxy-, ammonium salt (1:1), (2S)-

EC Number:

604-012-2

Cas Number:

137296-15-2

Molecular formula:

C3H9O3N

IUPAC Name:

Propanoic acid, 2-hydroxy-, ammonium salt (1:1), (2S)-

Specific details on test material used for the study:

Name of test material (as cited in study report): Ammonium Lactate, PURASAL® NH
- Physical state: yellowish-white liquid
- Analytical purity: not reported
- Lot/batch No.: 0503002615
- Expiration date of the lot/batch: 2007-09-28
- Storage condition of test material: room temperature (20 +/- 5 °C) in the dark
- Other: Reception date: 2005-04-01

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Interfauna Ibérica, S.L., Barcelona, Spain
- Age at study initiation: ca. 7-8 weeks
- Weight at arrival: 143-194 g
- Weight at study initiation: preliminary study: 215-233 g; main study: 212-235 g (males) and 200-221 g (females)
- Fasting period before study: 17-18 h prior to administration
- Housing: Makrolon cages with Ultrasorb sawdust bedding (Panlab S.L.); each cage contained up to 4 animals of the same sex; at the time of administration the rats were placed in individual cages with a grille floor to avoid contact with the sawdust or any other material that could cause cutaneous irritation.
- Identification of animals: individual indentification by code using an ear-punch technique
- Diet (e.g. ad libitum): standard rat diet, ad libitum
- Water (e.g. ad libitum): distilled water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 50-70
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ca. 24 hours before administration of the test item the back of each animal was shaved using an electric razor, from the scapula area to the lumbar region. the test item at a 100% concentration was placed on approximately 6.0 x 4.0 cm squares of hydrophillic gauze and applied to the corresponding test area.
- % coverage: 10% of the total body surface area.
- Type of wrap if used: The gauze was covered with a hypoallergenic microporous adhesive band. Finally, a strip of gauze was wrapped around the trunk of the rat in order to hold the patches in place. The band was fixed to the body of the animal using adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with distilled water
- Time after start of exposure: 24 h

TEST MATERIAL
- Concentration (if solution): 100%
- Dose: 2000 mg/kg bw; the amount of the test item administered to each animal was calculated taking into account its body weight at the time of administration.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

- Preliminary study: two male and two female rats per dose (2000 mg/kg bw)
- Main study: five male and five female rats per dose (2000 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration in preliminary and main study: 14 days
- Frequency of observations: twice daily
- Frequency of weighing: all rats were weighed before administration, halfway through the observation period, and before sacrifice
- Necropsy of survivors performed: yes (only animals of the main study)
- Other examinations performed: observations included, but were not limited to, changes in skin or fur, eyes and mucous membranes, respiratory, circulatory, central nervous and autonomic nervous systems, somatomotor activity and behaviour, in order to record any clinical response
- Sacrifice and postmortem procedures: at the end of the observation period, all the rats were sacrificed by intraperitoneal injection of sodium pentobarbital and then necropsies were performed on all the animals of the main study. The necropsy included a revision of the intact animal and all its superficial tissues, followed by an observation of the cranial, thoracic and abdominal cavities.

Statistics:

Statistics were performed on body weight (mean weight and standard deviation; see table 1)

Results and discussion

Preliminary study:

No mortality was recorded among the animals from the preliminary study (two males and two females) treated at the dose of 2000 mg/kg bw.
No clinical signs were recorded in any of the animals administered in the preliminary study on the day of administration nor on the following days.
No dermal alterations were recorded in any of the animals on removing the semi-occlusive patches.
The body-weight evolution in the treated males was normal. In the two females, a body-weight loss of 3 and 8 g, respectively, was recorded between the day of administration and day 7 of the observation period. In both cases, the animals regained weight.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality among the animals (5 males and 5 females) treated at the dose of 2000 mg/kg.

Clinical signs:

other: No clinical signs were recorded in any of the animals administered at the dose of 2000 mg/kg bw on the day of treatment nor during the observation period. No dermal alterations were recorded in any of the animals on removal of the semi-occlusive patches a

Gross pathology:

No macroscopic alterations were recorded in the necropsies done on all the animals from the main study.

Other findings:

N.A.

Any other information on results incl. tables

Table 1: Body weight (g), main study

Dose level (mg/kg)	Animal number	Sex	Day			Weights at necropsy
			0	7	10
2000	5	M	212	243	274	274
	6	M	217	245	268	268
	7	M	230	262	293	293
	8	M	224	260	292	292
	9	M	235	268	299	299
	Mean		223.6	255.6	285.2	285.2
	SD		9.34	11.01	13.41	13.41
	10	F	219	228	246	246
	11	F	203	211	224	224
	12	F	221	233	252	252
	13	F	200	209	223	223
	14	F	206	215	229	229
	Mean		209.8	219.2	234.8	234.8
	SD		9.58	10.69	13.33	13.33

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study conducted according to OECD guideline 402 rats were dermally treated with the test item. Based on the results, the LD50 can be considered to be greater than 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study (OECD 402, limit test), a group of young adult Sprague Dawley rats (5 males and 5 females) were dermally exposed to the test item (liquid, 100% concentration) for 24 hours to approximately 10% of body surface area at 2000 mg/kg bw. Animals were observed for 14 days. No mortality occurred. There were no treatment related clinical signs, necropsy findings or changes in body weight. The dermal LD50 value of the test item in both female and male Sprague Dawley rats was established to exceed 2000 mg/kg body weight.