[2-(1-ethoxyethoxy)ethyl]benzene

Endpoint summary

Description of key information

Acute oral toxicity (OECD TG 401): LD50 >5000 mg/kg bw

Acute dermal toxicity (OECD TG 402): LD50 >5000 mg/kg/ bw

Acute inhalation toxicity using route to route extrapolation from the oral route: > 13000 mg/m³

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:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Pre-GLP study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Weight at study initiation: 235-287 g
- Fasting period before study: 16-20 hours
- Housing: 5/cage in suspended wire mesh cages. Bedding was placed beneath the cages.
- Diet: fresh Purina Rat Chow (Diet #5012), ad libitum, except 16-20 hours prior to dosing
- Water: ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10 animals per dose

Control animals:

no

Details on study design:

- Frequency of observations: Animals were observed 3-4 hours post dosing and once daily thereafter for 14 days for mortality, toxicity and pharmacological effects.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, toxicity and pharmacological effects.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities.

Clinical signs:

other: none

Gross pathology:

none

Interpretation of results:

other: Not acute toxic

Remarks:

Based on EU CLP criteria (EC 1272/2008 and its updates)

Conclusions:

The acute oral LD50 of Hyacinth body for rats was >5000 mg/kg bw. Based on the results of this study it is concluded that Hyacinth body is not acute orally toxic.

Executive summary:

An acute oral toxicity study with Hyacinth body was performed according to a method similar to OECD TG 401, and was rated Klimisch 2 as it was performed comparable to guideline study with acceptable restrictions and it was pre-GLP. In this study, 10 rats were administered Hyacinth body at dose level 5000 mg/kg bw. None of the animals died. The acute oral LD50 for rats was therefore set at >5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

pre-GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Remarks:

Pre-GLP

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10 animals per dose

Control animals:

no

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities.

Clinical signs:

other: Slight redness: 3/10 Moderate redness: 5/10 Slight edema: 5/10 Moderate edema: 5/10

Gross pathology:

not specified

Other findings:

No further symptoms were noted.

Interpretation of results:

other: Not acute toxic

Remarks:

Based on EU CLP Criteria (EC 1272/2008 and its updates)

Conclusions:

An acute dermal toxicity study was performed with Hyacinth body according to a method similar to OECD TG 402. The dermal LD50 was therefore set at >5000 mg/kg/ bw. Based on the results of this study it is concluded that Hyacinth body is not acute dermally toxic.

Executive summary:

An acute dermal toxicity study was performed with Hyacinth body according to a method similar to OECD TG 402 and was rated Klimisch 2 as it was performed comparable to guideline study with acceptable restrictions and pre-GLP. In this study, 10 rabbits were dermally exposed to Hyacinth body at dose level 5000 mg/kg bw. There were no mortalities in this study. The clinical sign noted was a skin irritation demonstrated in slight to moderate redness (in eight animals in total) and slight to moderate edema (in all animals).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute oral toxicity

An acute oral toxicity study with Hyacinth body was performed according to a method similar to OECD TG 401, and was rated Klimisch 2 as it was performed comparable to guideline study with acceptable restrictions and it was pre-GLP. In this study, 10 rats were administered Hyacinth body at dose level 5000 mg/kg bw. None of the animals died. The acute oral LD50 for rats was therefore set at >5000 mg/kg bw.

A number of other studies are available, they are considered supporting to the results described in above mentioned key study. In a study by PFW, (1976a) similar to OECD 401, an LD50 > 5 g/kg in rabbits was reported. Furthermore, Givaudan, (1971p); OECD 401 reported that 5 g/kg was lethal in 1/10 rats on day 13, but there were no signs of toxicity. Necropsy revealed a mottled liver, dark lungs, small intestine and red stomach in one animal. A fourth study by Quest, (1977o) reported an LD50 > 10 ml/kg.

Acute dermal toxicity

An acute dermal toxicity study was performed with Hyacinth body according to a method similar to OECD TG 402 and was rated Klimisch 2 as it was performed comparable to guideline study with acceptable restrictions and pre-GLP. In this study, 10 rabbits were dermally exposed to Hyacinth body at dose level 5000 mg/kg bw. There were no mortalities in this study. The clinical sign noted was a skin irritation demonstrated in slight to moderate redness (in eight animals in total) and slight to moderate edema (in all animals).

Acute inhalation toxicity

Acute inhalation is predicted based on the acute oral toxicity in accordance with the ECHA CLP guidance document (2017, Section 3.1.3.3.5, pg 250: 1 mg/kg bw = 0.0052 mg/L (5.2 mg/m³). The acute inhalation is predicted to be > 13000 mg/m³ (using 100% inhalation and 50% oral absorption and an LD50 oral of > 5000 mg/kg bw). The calculated saturated vapour concentration is 247 mg/m3 (at 24 ºC and 1 atmosphere), using the following formula: MW * VP (in Pa) * 1000 (g to mg) / [(8.3 (gas constant) * 293 (°K)] = 194.28 * 3.1 * 1000/ (8.3 * 293). This means that the acute inhalation concentration cannot be reached and therefore no acute inhalation toxicity is anticipated.

Justification for classification or non-classification

Based on the available data it is concluded that Hyacinth body does not need to be classified for acute oral, dermal and inhalation toxicity in accordance with EU CLP (EC No. 1272/2008 and its amendments)