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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-05-18 to 2005-06-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

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: 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: 2005-09-28

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

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. 9 weeks (animals were ca. 8 weeks at arrival at the test facility and underwent a 7 day acclimatisation period prior to study initiation)
- Weight at study initiation: preliminary study (2 animals): 207 and 218 g; main study (5 animals): 206-221 g
- Fasting period before study: 17-18 h prior to administration
- Housing: Makrolon cages with Ultrasorb sawdust bedding (Panlab S.L.); each cage contained a maximum of 5 animals of the same sex and administration group; the sawdust bedding was replaced by a metal grille during the period of fasting previous to administration
- Identification of animals: individual indentification by code using an ear-punch technique
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 45-70
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Lot/batch no. (if required): 5133B02

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

Preliminary study:
The test item was administered orally to two females. Initially, one rat was treated at the dose of 300 mg/kg bw. As neither mortality nor clinical signs were observed in this animal, another animal was treated at the dose of 2000 mg/kg bw.

Main study:
Based on the information obtained in the preliminary study, and since neither mortality nor signs of toxicity were recorded in the female administered at the dose of 2000 mg/kg, the test item was administered orally at the dose of 2000 mg/kg bw to four more animals, making a group of five animals treated in the main study.

No. of animals per sex per dose:

Preliminary study: 1 animal per dose (300 and 2000 mg/kg bw)
Main study: 5 animals per dose (2000 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
* Preliminary study: observations at least twice daily
* Main study: at the day of administration the animals were observed frequently in order to record any possible clinical signs; afterwards the rats were observed at least twice daily for 14 days
- Weighing: before administration, daily on the three following days after treatment, weekly afterwards, and before sacrifice
- Necropsy of survivors performed: yes. 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. This included the inspection of the intact animal and all superficial tissues,
followed by the observation of the viscera of the cranial, thoracic and abdominal cavities.
- Other examinations performed: changes in skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern in order to note any possible clinical response.

Statistics:

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

Results and discussion

Preliminary study:

Initially, one rat was treated at the dose of 300 mg/kg body weight. As neither mortality nor clinical signs were observed in this animal, another animal was treated at the dose of 2000 mg/kg bw. Piloerection was recorded in this animal from 3-4 hours after the administration. The presence of this clinical sign was not considered enough to confirm that the animal presented evident toxicity. This animal did not present clinical signs on the days following the treatment. No macroscopic alterations were recorded at the necropsies performed on the animals treated at the cited doses.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: None

Gross pathology:

No macroscopic alterations were detected during the necropsies done on the animals treated at the dose of 2000 mg/kg bw.

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 of the observation period						Weight at necropsy
			0	1	2	3	7	14
2000	2	F	218	240	235	233	238	253	253
	3	F	221	244	246	248	258	265	265
	4	F	217	243	245	249	249	251	251
	5	F	206	222	226	226	228	238	238
	6	F	211	233	235	235	251	264	264
	Mean		214.6	236.4	237.4	238.2	244.8	254.2	254.2
	SD		6.02	9.13	8.26	9.98	11.82	11.03	11.03

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study conducted according to OECD guideline 420, rats were orally 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 oral toxicity study conducted according to OECD guideline 420, five female Sprague Dawley SD rats were given a single oral dose of the test item in distilled water at a dose of 2000 mg/kg bw. The animals were observed for 14 days after the single exposure. No clinical signs and no mortalities occurred. Therefore, the oral LD50 can be considered to be greater than 2000 mg/kg bw.