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

Endpoint summary

Description of key information

In an acute oral toxicity study conducted according to OECD 420 and in an acute dermal toxicity study conducted according to OECD 402 young adult rats were exposed to the target substance. No mortality occurred after a single application of 2000 mg/kg bw in both studies within a 14 days observation period. Based on the results both the oral and the dermal LD50 exceed 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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

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).

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.

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.

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

GLP guideline study conducted according to OECD 420 conducted with the target substance.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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

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

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)

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.

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.

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

GLP guideline study conducted according to OECD 402 conducted with the target substance.

Additional information

Data from two acute toxicity studies conducted with the target substance are available. In an acute dermal toxicity study (OECD 402, limit test), a group of young adult Sprague Dawley rats (5 animals per sex) were dermally exposed to the target substance for 24 hours to approximately 10% of body surface area at 2000 mg/kg bw. Animals were observed for 14 days. No mortality occurred and the LD50 was considered to exceed 2000 mg/kg bw.

Furthermore, 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 target substance at a dose of 2000 mg/kg bw. The animals were observed for 14 days and no clinical signs and/or mortalities occurred. Therefore, the oral LD50 can be considered to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data the target substance does not warrant classification for acute toxicity. The LD50 values for both the dermal and the oral route are above the limit dose of 2000 mg/kg bw of CLP Regulation (EC) No 1272/2008.