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Description of key information

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:
10/03/1983 - 28/03/1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed in a toxicological institute under supervision of a veterinarian. Even though, no specific guideline was followe the test was performed similar to the OECD guideline 423.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
Winkelmann, Borchen
- Age at study initiation:
males: 48-51 days;
females: 59 days
- Weight at study initiation:
males: 0.127 - 0.139 kg
females: 0.128 - 0.134 kg
- Fasting period before study:
16 hours before start of the test
- Housing:

- Diet (e.g. ad libitum):
ad libitum
- Water (e.g. ad libitum):
ad libitum
- Acclimation period:
5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
21 +- 2
- Humidity (%):
55 +- 5
- Photoperiod (hrs dark / hrs light):
12/12
Route of administration:
oral: gavage
Vehicle:
other: tragacanth
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
238 mg/ml
- Amount of vehicle (if gavage):
21.5 ml/kg

Doses:
5110 mg/kg
No. of animals per sex per dose:
5
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 110 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured during the observation period of 14 days.
Clinical signs:
no adverse clinical signs observed
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
GHS criteria not met
Conclusions:
L-Histidine does not show acute toxicity in rats at a concentration of 5110 mg/kg.
Executive summary:

In this study the acute toxicity of L-histidine was assessed in a similar way as in the OECD Guideline 423, in rats via gavage.

Five animals were dosed with a dose of 5110 mg/kg, whereafter they were observed for 14 days.

No mortality occured and no adverse clinical signs were observed.

Even though no NOAEL was determined in this study, the results indicate that there were no effects at a concentration of 5110 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 110 mg/kg bw
Quality of whole database:
Remark: No mortalities occurred in any of the experiments. The LD50 is therefore > 5110 mg/kg bw. However, this result cannot be entered in the preceding field.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No studies are available for acute toxicity via dermal or inhalation route. In accordance with column 2 of REACH Annex VIII testing on acute toxicity by inhalation or dermal route is only required if exposure of humans via this route is likely taking into account the physicochemical properties of the substance (such as vapour pressure, water solubility, volatility and lipophilicity).

In the case of L-histidine, exposure via the inhalation or dermal route is not considered to be of concern.

Regarding acute toxicity via oral route, two studies are available. In the first study (key - Mayr, 1983) the acute toxicity of L-histidine was assessed in rats via gavage. The methodology was similar to the OECD Guideline 423. The animals were dosed with 5110 mg/kg and observed for 14 days thereafter. No mortality occured and no adverse clinical signs were observed.

In the second study (supporting - Davies and Halliday, 1971), the acute toxicity of L-histidine was also assessed in rats, not following an OECD. Rats were fed a dose of 16000 mg/kg bw and oberved for 2 weeks thereafter. No animals died and the autopsy did not reveal abnormalities.

Taken toghether, the NOAEL is 5110 mg/kg and the LD50 > 5110 mg/kg.


Justification for selection of acute toxicity – oral endpoint
The study was performed in a toxicological institute under supervision of a veterinarian, and was similar to the OECD guideline 423. It was well documented and conducted.

Justification for classification or non-classification

The criteria for classification of acute toxicity according to the CLP regulation No 1272/2008 take into account the LD/LC50 values as the acute toxicity estimates (ATE). Using the ATE, the substance can be allocated to one of the four toxicity categories shown in Table 3.1.1 in Part 3: Health hazards of the CLP Regulation.

As the LD50 for L-histidine > 5110 mg/kg bw which is higher than the highest level in category 4 (2000 mg/kg bw), L-histidine does not require to be classified according to the criteria of the CLP regulation.