2,5-dichloro-4-[[2-(dibutylamino)-4-methyl-6-[[2-(4-sulphophenyl)ethyl]amino]-5-pyrimidinyl]azo]benzenesulphonic acid, sodium salt

Endpoint summary

Description of key information

Oral LD50 (female) > 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:

From 05 to 24 September, 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

The complete study report is not available, thus some details about test conditions are missing.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 December 2001

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 189 - 255 g
- Fasting period before study: fasted females were used; no details about the fasting period.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

A group of three fasted females was treated with the test materia; this was followed by a further group of three fasted female animals at the same dose level.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females (three animals per step)

Details on study design:

Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths or signs of systemic toxicity.

Gross pathology:

No abnormalities detected.

Individual Bodyweights and Weekly Bodyweight Changes

Dose Level mg/kg	Animal N. and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	1-0 Female	220	241	258	21	17
	1-1 Female	255	299	314	44	15
	1-2 Female	192	216	242	24	26
	2-0 Female	206	230	246	24	16
	2-1 Female	199	228	236	29	8
	2-2 Female	189	220	230	31	10

Interpretation of results:

other: not classified, according to the CLP Regulation (EC) No 1272/2008

Conclusions:

LD50 (female) > 2000 mg/kg bw

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 Crl:CD^(R) (SD) IGS BR rat. The method followed the OECD Guidelines No. 423.

A group of three fasted females was treated with the test material at a dose level of 2000 m/kg bw. This was followed by a further group of three fasted female animals at the same dose level. The test material was administered orally as a suspension in distilled water. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths or signs of systemic toxicity. The acute oral median lethal dose (LD50) of the test material, in the rat, was estimated as being greater than 2000 mg/kg bodyweight.

Conclusion

LD50 (female) > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

ACUTE TOXICITY - ORAL ROUTE

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in female rats. The method followed the OECD Guidelines No. 423. No deaths or signs of systemic toxicity were recorded during the exposure and observation periods. The acute oral median lethal dose (LD50) of the test material was estimated as being greater than 2000 mg/kg bodyweight.

ACUTE TOXICITY - INHALATION ROUTE

No acute toxicity studies by inhalation route are available on Acid Yellow 236.

Nevertheless, because of the physical state of the substance inhalation is not an appropriate route of exposure. Particle size distribution showed that the ca 99 % of particles has a diameter greather than 100 µm. Thus, most of the Acid Yellow 236 particles are expected to remain in the upper respiratory tract, which is characterized by efficacious defence mechanisms able to remove them; therefore, respirable particles, able to enter the deepest part of the lung, the non-ciliated alveoli (i.e. D50 of 4 µm), can be considered a minimal portion. This consideration, together with the consideration that the substance is manufactured and handled with suitable risk management measures and with the suitable personal protective equipments, lets to consider the possible absorption of the substance by inhalation route as negligible.

ACUTE TOXICITY - DERMAL ROUTE

According to the Commission Regulation (EU) No 2016/863, amending Annexes VII and VIII to REACH Regulation (EC) No 1907/2006, testing by the dermal route does not need to be conducted if no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation). 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, no signs of systemic toxicity were recorded.

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 2000 mg/kg body weight (based on active ingredient), 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 route toxicities are not expected; however, no specific acute toxicity investigations are available and none is required.

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