Registration Dossier

Administrative data

Description of key information

Oral LD50 (male and female) > 5000 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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 3rd to 29th March, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
The test substance is the acid form of the substance under registration; justification for Read Across is detailed in the IUCLID section 13.
Reason / purpose:
read-across source
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Specific details on test material used for the study:
For the purpose of this study the test material was ground to a fine powder using a mortar and pestle freshly prepared.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna (UK) Limited, Wyton, Huntingdon, Cambridgeshire.
- Age at study initiation: at the start of the main study the males weighed 174 - 192 and the females 150 - 161 gg
- Weight at study initiation: at the start of the main study the rats were approximately five to eight weeks old.
- Fasting period before study: over-night fast immediately before dosing and for approximately two hours after dosing.
- Housing: the animals were housed in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet: Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K, ad libitum.
- Water: drinking water, ad libitum.
- Acclimation period: minimum five days.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 22 °C
- Humidity: 39 - 45 %
- Air changes: approximately 15 changes per hour.
- Photoperiod: lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
RANGE-FINDING
The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Vehicle: distilled water.
Cocnentration: 200 and 500 mg/ml.
Dose volume: 10 ml/kg

MAIN TEST
Vehicle: distilled water.
Cocnentration: 500 mg/ml.
Dose volume: 10 ml/kg
Doses:
RANGE-FINDING: 2000 and 5000 mg/kg bw
MAIN TEST: 5000 mg/kg bw
No. of animals per sex per dose:
RANGE-FINDING: 1 male and 1 female per group.
MAIN TEST: 5 male and 5 female per group.
Details on study design:
RANGE-FINDING
A preliminary study was performed using pre-selected dose levels to determine the highest of these dose levels that produced a mortality rate of less than 50 % as follows.
One male and one female were dosed at 5000 mg/l and another one male and one female were desed at 2000 mg/kg.
Animals were observed 1 and 4 hours following dosing‘and then once daily for five days. Deaths and evidence of overt toxicity were recorded at each observation. No necropsies were performed.

MAIN TEST
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Deaths and evidence of overt toxicity were recorded at each observation. Individual bodyweights were recorded on the day of dosing (day 0) and, on days 7 and 14.
- Necropsy of survivors performed: all animals were subjected to gross necropsy examination for any macroscopic abnormalities. No tissues were retained.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No deaths occurred.
Clinical signs:
All treated animals appeared normal during the study period.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were detected at necropsy of animals kilied at the end of the study.

Individual bodyweights and weekly bodiweight increases in the main study

Dose level (mg/kg) Animal number and sex Bodyweight (g) at day Increment (g) during week
0 7 14 1 2
5000 3-0 M 179 254 312 75 58
3-1 M 174 262 326 88 64
3-2 M 192 286 356 94 70
3-3 M 176 260 323 84 63
3-4 M 177 244 292 67 48
4-0 F 152 198 220 46 22
4-1 F 161 197 222 36 25
4-2 F 154 190 214 36 24
4-3 F 151 193 220 42 27
4-4 F 150 190 216 40 26
Interpretation of results:
other: not classified, according to the CLP Ragulation (EC) No 1272/2008
Conclusions:
LD50 > 5000 mg/kg bw (males and females)
Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley rat. The method followed the OECD Guidelines 401 (1981). A preliminary study was performed unsing pre-selceted doses of 2000 amd 5000 mg/kg bw; the highest of the two doses that produce a mortality rate of less than 50 % was selected for the main test.

In the main experiment, a group of five males and five females was treated with 5000 mg/kg bodyweight. The test material was administered orally by gavage.

No deaths occurred and no signs of systemic toxicity were noted during the study.

Conclusion

LD50 > 5000 mg/kg bw (males and females)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

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

ACUTE TOXICITY, ORAL ROUTE

There are no information about the oralacute toxicity potentialof Basic Orange 064, thus the available information on the structural analogous Similar Substance 01 have been taken into consideration. Similar Substance 01 is the acid form of Basic Orange 064; the read across approach can be considered as appropriate and suitable to assess the property under investigation (details about the approach are reported into the IUCLID section 13).

The study was performed to assess the acute oral toxicity of Similar Substance 01, following the OECD Guidelines 401 (1981) testing procedures. A preliminary study was performed unsing pre-selceted doses of 2000 amd 5000 mg/kg bw. In the main experiment, the test material was administered orally by gavage at 5000 mg/kg bw.

No deaths occurred and no signs of systemic toxicity were noted during the study.

ACUTE TOXICITY, INHALATION ROUTE

No acute toxicity studies by inhalation route are available on Basic Orange 064.

Nevertheless, because of the physical state and the trade forms of the substance under registration, inhalation is not an appropriate route of exposure. Acute toxicity results for the other exposure routes indicate no concern.

ACUTE TOXICITY, DERMAL ROUTE

The inhalation and the skin contact of Basic Orange 064 are unlikely.

Extend of percutaneous absorption of a substance depends largely on the physical and chemical properties of the substance itself. In particular, factors like the degree of ionization, molecular size and water and lipid solubilities influence penetration through the skin. Considering the molecular size and the hydrophilic character of Basic Orange 064, dermal route is not expected to be the main absorption route.

According to the REACH Regulation, Annex VIII, Column 1 Standard information required, testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation).

Furthermore, in the Commission Regulation (EU) 2016/863, amending Annexes VII and VIII to REACH Regulation (EC) No 1907/2006, it is explained that recent scientific analysis of available data from in vivo acute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. Therefore, testing those substances via the dermal route does not provide essential information for their safety assessment.

The amendment is the consequence of studies and scientific debates. In particular, the 15th Meeting of Competent Authorities for REACH and CLP (CARACAL, 2014) concluded that an adaptation of point 8.5.3 of Annex VIII to REACH is justified in order to not require information on acute dermal toxicity for substances that have shown no toxicity in acute oral toxicity test up to the limit dose of 2000 mg/kg bw.

In the oral acute toxicity test performed on the structural analogous Similar Susbtance 01 no signs of systemic toxicity were recorded. The skin sensitisation potential was investigated in Guinea Pig Maximization Test conducted on Similar Substance 02 and no test item-related systemic clinical signs were observed.

Justification for classification or non-classification

According to the CLP Regulation (EC) No 1272/2008, 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be greater than 5000 mg/kg body weight, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity category 4: 300 < ATE ≤ 2000 mg/kg bw).

 

Dermal and inhalation exposure is unlikely, thus no acute toxicity value is available and no further investigation is required.

 

In conclusion, the test substance is non classified for oral acute toxicity, according to the CLP Regulation (EC) No 1272/2008.