Carnosine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1991

Materials and methods

GLP compliance:

no

Test material

Test material information

1

Reference substance name:

Zinc (2S)-2-(β-alanylamino)-3-(imidazol-1-id-4-yl)propanoate

EC Number:

600-848-7

Cas Number:

107667-60-7

Molecular formula:

C9H12N4O3Zn

IUPAC Name:

Zinc (2S)-2-(β-alanylamino)-3-(imidazol-1-id-4-yl)propanoate

Test animals

Species:

other: rat

Strain:

other: rat: Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 weeks
- Weight at study initiation: rat (male): 102 - 156 g, rat (female): 87 - 133 g
- Fasting period before study: overnight before dosing
- Diet: CRF-1 (Oriental Yeast Co.), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 40 - 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5%

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:

rat: 0; 4823; 5787; 6944; 8333; 10000 mg/kg bw

No. of animals per sex per dose:

10 animals per sex per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed daily, Individual body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7, 10 and 14 after dosing.
- Necropsy of survivors performed: yes
All organs and tissues were examined macroscopically. Any macroscopically abnormal tissue was preserved in 10% neutral buffered formalin.

Statistics:

The approximate LD50 and 95 % confidence limit were estimated from the mortality rate during the observation period by Probit method.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Remarks:

rat

Effect level:

ca. 7 000 - ca. 8 500 mg/kg bw

Based on:

test mat.

Mortality:

Rat: Death occured from day 1 to day 5 after oral administration.

Clinical signs:

other: Rats showed a decrease in locomotor activity, ventral posture, crouching, hypothermia and/or respiratory depression after administration of test substance. The signs disappeared 2 - 4 days later in surviving animals. In addition, loose feces and dirtiness

Gross pathology:

The necropsy findings were as follows: After oral administration, rats showed a test article-like substance in the gastrointestinal tract, erosion of the glandular stomach mucosa and congestion in the lung. In addition to these changes, ulcer in the forestomach mucosa, ulcer or erosion in the glandular stomach mucosa and enlargement of the stomach were observed in dead rats. Surviving animals showed no abnormalities following dosing by the oral route. The changes in the gastrointestinal tract of dead animals dosed by the oral route were considered to be caused by the deteriorating general condition of these animals during the 2-3 days prior to death.

Other findings:

No sex differences have been observed.

Any other information on results incl. tables

Table 1: Acute Toxicity: oral

Animal	Dose (mg/kg bw)	Sex	Mortality	LD50 (mg kg bw) (95% confidence limit)
Rat	0	male	0/10	8441 (7274 – 11746)
	4823		0/10
	5787		3/10
	6944		3/10
	8333		4/10
	10000		7/10
	0	female	0/10	7375 (6556 – 8544)
	4823		0/10
	5787		3/10
	6944		5/10
	8333		5/10
	10000		9/10

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute oral toxicity study in rats a LD50 value of ≥ 7000 mg/kg bw was derived.
CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Executive summary:

Acute oral toxicity study in rats (Sprague-Dawley) were conducted with the read-across (RA) substance catena-(S)­ [µ-[Nα-(3-Aminopropionyl)histidinato(2-)-N1,N2,0:Nτ]- zinc], (CAS 107667 -60 -7) and was used as supporting study.

The RA substance was administered at doses of 0, 4823, 5787, 6944, 8333, 10000 mg/kg bw to rats (one male and one female per dose)

During a period of 14 days following administration, the animals were observed daily and individual body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7, 10 and 14 after dosing.

3, 3, 4 and 7 female rats were found dead at the applied doses of 5787, 6944, 8333 and 10000 mg/kg bw, respectively. 3, 5, 5 and 9 male rats were found dead at the applied doses of 5787, 6944, 8333 and 10000 mg/kg bw, respectively. Death was observed 1 to 5 days after oral administration of the RA substance. The LD50 value for rats was calculated to be 7000 -8500 mg/kg bw.

Rats showed a decrease in locomotor activity, ventral posture, crouching, hypothermia and/or respiratory depression after administration of the test substance. The signs disappeared 2 - 4 days after administration in surviving animals. In addition, loose feces and dirtiness of fur following oral dosing were observed in rats. These signs disappeared 5 - 6 days later in surviving animals.

Under the condition of the acute oral toxicity test with the RA substance zinc-carnosine (CAS 107667 -60 -7), the determined LD50 value for rats does not meet the criteria for classification according to Regulation (EC) 1272/2008.