2,6-diisopropylnaphthalene

Endpoint summary

Description of key information

Acute oral toxicity (OECD 401): LD50 (rat, m/f) > 5000 mg/kg bw

Study performed with 2,6-diisopropylnaphthalene (CAS No. 24157-81-1)

Acute inhalation toxicity (OECD 403): LC50 (rat, m/f) > 5.64 mg/L air

Read-across from analogue source substance bis(isopropyl)naphthalene (CAS No. 38640-62-9)

Acute dermal toxicity (OECD 402): LD50 (rat, m/f) > 4500 mg/kg bw

Read-across from analogue source substance bis(isopropyl)naphthalene (CAS No. 38640-62-9)

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:

21 Jul - 04 Aug 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA, USA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adults
- Weight at study initiation: 218 - 230 g (males), 161 - 170 g (females)
- Fasting period before study: approx. 24 h
- Housing: Singly housed in suspended stainless steel cages with mesh floors
- Diet: Purina Rodent Chow #5012, no further details given
- Water: Filtered tap water, ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9 - 22.8
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 21 July To: 04 Aug 1997

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% (w/w)
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: Preliminary solubility testing indicated that suspensions in excess of 50% were too viscous to be administered.

MAXIMUM DOSE VOLUME APPLIED: 2.4 mL

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1 and 3 h post dosing, at least once daily until termination
- Frequency of weighing: prior to dosing, Day 7 and Day 14 before termination or after death
- Necropsy of survivors performed: yes
- Observations: Gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention to tremors, convulsions, salivation, diarrhea and coma.
- Necropsy: Tissues and organs of the thoracic and abdominal cavities.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

act. ingr.

Mortality:

One female died 6 days after test substance administration.

Clinical signs:

Clinical signs included hunched posture, hypoactivity, piloerection, reduced fecal volume, facial and/or ano-genital staining. The surviving animals recovered from clinical signs by Day 7.

Body weight:

All surviving animals gained bodyweight over the 14-day observation period.

Gross pathology:

Gross necropsy of the female found dead on Day 6 revealed discoloration of the lungs and intestines. Gross necropsy findings for the surviving animals at terminal sacrifice were generally unremarkable.

Table 1: Individual bodyweight, dosage and mortality

Animal no.	Sex	Bodyweight [g]			Dose [mL]	Mortality
		Initial	Day 7	Day 14		Day	Bodyweight [g]
8762	M	227	263	334	2.4	E	--
8763	M	230	248	324	2.4	E	--
8764	M	218	257	317	2.3	E	--
8765	M	221	250	307	2.3	E	--
8766	M	218	254	302	2.3	E	--
8767	F	167	204	226	1.7	E	--
8768	F	162	--	--	1.7	6	152
8769	F	161	189	214	1.7	E	--
8770	F	170	190	214	1.8	E	--
8771	F	163	202	222	1.7	E	--

M: Male

F: Female

E: Euthenised on Day 14

Table 2: Individual cage-side observations

Animal no.	Findings	Day of occurrence
8762 (M)	Active and healthy Hypoactivity Hunched posture Piloerection	0(1-3 h), 5-14 0(21 h)-2 0(21 h)-3 0(21 h)-4
8763 (M)	Active and healthy Piloerection, hunched posture Hypoactive Facial staining Ano-genital staining	0(1-3 h), 7-14 0(21 h)-4 1-2 2 2-6
8764 (M)	Active and healthy Piloerection	0(1-21 h), 3-14 1-2
8765 (M)	Active and healthy Hypoactive Hunched posture Piloerection Facial staining Ano-genital staining	0(1-3 h), 6-14 0(21 h)-2 0(21 h)-3 0(21 h)-4 2 2-3, 5
8766 (M)	Active and healthy Hunched posture Piloerection Hypoactive Facial staining	0(1-3 h), 6-14 0(21 h)-4 0(21 h)-5 1-2 2
8767 (F)	Active and healthy Hypoactive Piloerection, hunched posture Reduced vecal volume	0(1-3 h), 6-14 0(21 h) 0(21 h)-4 2, 5
8768 (F)	Active and healthy Piloerection Hunched posture, reduced fecal volume Hypoactive Dead	0(1-21 h) 1-5 2-5 3-5 6
8769 (F)	Active and healthy Piloerection Hunched posture Hypoactive Reduced fecal volume	0(1-21 h), 6-14 1-3 1-4 2-3 2-5
8770 (F)	Active and healthy Piloerection, hunched posture Facial staining, hypoactive Reduced fecal volume Ano-genital staining	0(1-3 h), 4-5, 7-14 0(21 h)-3 1 1-3, 6 6
8771 (F)	Active and healthy Piloerection Hunched posture Reduced fecal volume	0(1-21 h), 6-14 1-3 2-3 2-5

M: Male

F: Female

Table 3: Individual necropsy observations

Animal no.	Tissue	Findings
Males
8762-8766	Lungs	Slightly red*
Females
8767, 8769-8771	Lungs	Slightly red*
8768	Lungs Intestines	Slightly red* Red

*: Customarily seen with CO₂ inhalation, due to euthanasia procedure.

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 > 5000 mg/kg bw was determined.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 1) study performed with the registered substance. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, Item 8.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Refer to the analogue approach justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.64 mg/L air

Based on:

test mat.

Remarks:

(aerosol)

Exp. duration:

4 h

Remarks on result:

other: Source: CAS No. 38640-62-9, Bernstein, 1988

Interpretation of results:

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

Conclusions:

An inhalation LD50 value of > 5.64 mg/L air was determined for male and female rats after exposure to an aerosol of the source substance for 4 h.

Executive summary:

The acute inhalation toxicity of the target substance is predicted based on an adequate and reliable in vivo study of a structural analogue source substance. The inhalation LD50 value determined in the limit test was > 5.64 mg/L air for male and female rats after a 4 h exposure period to an aerosol of the test substance. No hazard for the target substance is identified and classification and labelling is set accordingly. As explained in the analogue justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the acute inhalation toxicity.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 1) study from a source substance with similar structures and intrinsic properties. Read-across is justified based on a common metabolic breakdown of target and source substances. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, Item 8.5, in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Refer to the analogue approach justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: only one dose administered (limit test); no mortality

Remarks:

Source: CAS No. 38640-62-9, Meisel, 1984

Interpretation of results:

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

Conclusions:

An LD50 value > 2000 mg/kg bw has been determined for male and female rats.

Executive summary:

The acute dermal toxicity of the target substance is predicted based on an adequate and reliable in vivo study with a structural analogue source substance. The LD50 value determined experimentally is > 4500 mg/kg bw for male and female rats. Therefore, a LD50 value of > 2000 mg/kg bw for the target substance is considered for the hazard assessment and classification and labelling. As explained in the analogue justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 1) study from a source substance with similar structures and intrinsic properties. Read-across is justified based on a common metabolic breakdown of target and source substances. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, Item 8.5, in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006.

Additional information

Only data on acute oral toxicity is available for 2,6-diisopropylnaphthalene (CAS No. 24157-81-1). The endpoints acute inhalation and acute dermal toxicity are, therefore, assessed by means of read-across from the analogue source substance bis(isopropyl)naphthalene (CAS No. 38640-62-9).

Acute oral toxicity

The acute oral toxicity of 2,6-diisopropylnaphthalene (CAS No. 24157-81-1) was investigated in a limit test according to OECD guideline 401 (Wnorowsky, 1997). Groups of 5 Sprague-Dawley rats per sex were administered a single dose of 5000 mg/kg bw by oral gavage. Animals were observed for a period of 14 days post administration. Following administration, one female was found dead on Day 6. The death was preceded by clinical signs incl. hunched posture, hypoactivity, piloerection, reduced fecal volume, facial and/or ano-genital staining. Clinical signs were also observed in the surviving animals. All surviving animals completely recovered from clinical signs by Day 7 and gained bodyweight over the 14-day observation period. Gross necropsy of the female found dead on Day 6 revealed discoloration of the lungs and intestines. Gross necropsy findings for the surviving animals at terminal sacrifice were generally unremarkable. Based on these findings, the LD50 value was determined to be > 5000 mg/kg bw for male and female rats.

Acute inhalation toxicity

In an acute inhalation toxicity test using only one concentration (5.64 mg/L air, limit test), 5 Wistar rats/sex were exposed to an aerosol of bis(isopropyl)naphthalene (CAS No. 38640-62-9) for 4 h. The study was conducted according to OECD guideline 403 and observed GLP conditions (Bernstein, 1988). The post-dosing observation period was 14 days. The lungs from all animals were collected at necropsy and fixed in a neutral phosphate buffered 4% formaldehyde solution for further examination. Clinical signs during exposure included light to moderate nose bleeding (epistaxis) while after exposure slight to moderate signs of discomfort and physiological distress, hunched posture, piloerection, distended abdomen, tremor, impaired breathing, salivation and rhinorrhea were observed. Impaired breathing and piloerection continued until the end of the observation period. Rales were observed starting at Day 2 and continued into Week 2 of observation. Symptoms were more pronounced in females than in males. The mean body weight of the males decreased from test Day 1 to Day 8 for males. Until test Day 15, mean body weights increased again but did not reach their initial (pre-dose) levels. In females, the mean body weight decreased continuously to Day 15. Upon necropsy, red spots were found in the lungs of the animals. Two of the female rats died at Day 14 (mortality 2/10 total). The LC50 for acute inhalation toxicity was established to be > 5.64 mg/L air.

Acute dermal toxicity

The acute dermal toxicity of bis(isopropyl)naphthalene (CAS No. 38640-62-9) was examined in a study according to OECD guideline 402 and observing GLP provisions (Meisel, 1984). 5 Sprague-Dawley rats per sex were exposed to a dose of 4500 mg/kg bw of the unchanged test material for 24 h under occlusive conditions and subsequently observed for a period of 14 days. No mortality occurred and no clinical or gross pathological findings were observed. The LD50 for acute dermal toxicity of the test material was, therefore, determined to be > 4500 mg/kg bw.

Justification for classification or non-classification

The available data on the oral acute toxicity of 2,6-diisopropylnaphthalene (CAS No. 24157-81-1) as well as the data on inhalation and dermal toxicity for the analogue source substance bis(isopropyl)naphthalene (CAS No. 38640-62-9) do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP). Data are, therefore, conclusive but not sufficient for classification. Based on an analogue read-across approach, the target substance 2,6-diisopropylnaphthalene (CAS No. 24157-81-1) also does not warrant classification for acute inhalation and dermal toxicity.