Registration Dossier

Administrative data

Description of key information

The studies available for 2,4,4-trimethylpentene indicate a substance of low oral and dermal toxicity.  Information from diisobutylene (a less pure form) indicate that low acute toxicity by inhalation is also likely for 2,4,4-trimethylpentene.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD (remote Sprague-Dawley origin)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England
- Age at study initiation: Approximately 5 weeks
- Weight at study initiation (day -1): 122-133 g (males); 118-134 g (females)
- Fasting period before study: overnight prior to dosing and 4 hours following dosing
- Housing: Stainless steel grid cages . Five animals of the same sex / cage.
- Diet: Complete pelleted rodent diet (RM1(E) SQC, from Special Diets Services Limited, Witham, Essex, England ad libitum except overnight prior to, and for 4 hours after, dosing.
- Water: Tap water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-28°C
- Humidity: 54-70%
- Air changes: At least 10/hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 23 May 1996 To: 6 June 1996
Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Prepared at the appropriate concentration in maize oil to permit administration at a constant volume-dosage of 10 mL/kg
Doses:
2000 mg/kg bodyweight
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 and weighing: Observations were recorded 3 times on day 1 and daily thereafter. Bodyweights were recorded on the day before dosing and on days 1,8 and 15
- Necropsy of survivors performed: yes
Statistics:
Not applicable (limit test, no mortalities)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortalities
Clinical signs:
No abnormalities
Body weight:
All animals achieved anticipated bodyweight gains
Gross pathology:
There was a single case of hydronephrosis of the kidney
Interpretation of results:
other: low oral toxicity
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dosage (LD50) of 2,4,4-trimethylpentene was greater than 2000 mg/kg. 2,4,4-Trimethyl pentene is considered to be of low oral toxicity.
Executive summary:

A group of 5 male and 5 female CD rats (fasted overnight) were dosed by gavage at 2000 mg/kg of 2,4,4 -TMP (in maize oil) and were observed daily for 14 days after dosing. Bodyweights were recorded weekly during the observation period. There were no mortalities and no signs of toxicity. All animals gained weight and there were no significant necropsy findings. The acute oral median lethal dosage (LD50) of 2,4,4-trimethylpentene was greater than 2000 mg/kg. 2,4,4-trimethyl pentene is considered to be of low oral toxicity and does not require classification under DSD or CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Adequate information is available to characterise the short-term hazards of this substance

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD®(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, North Carolina, USA
- Weight at study initiation: males 261-276 g; females 202-213 g
- Age at study initiation: males Approximately 8 weeks
- Fasting period before study:
- Housing: Individual suspended wire-mesh cages except during inhalation when they were placed in a wire-mesh battery containing 10 separate cages
- Diet: PMI Nutrition International, LLC, Certified Rodent Lab Diet® 5002 ad libitum except during exposure
- Water: Municipal water ad libitum except during exposure
- Acclimation period: Minimum of 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21.2-21.7°C
- Humidity: 41.7-53.7%
- Air changes (per hr): Not reported
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 8 November 2005 To: 22 November 2005
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposure apparatus: 130 L glass and stainless steel whole-body inhalation chamber operated at a minimum of 10 air changes per hour. Exposure atmosphere conditions were recorded approximately every 30 minutes during the exposure. Oxygen content was measured pre-exposure. The time required to attain 99% of the equilibrium concentration (or clearance time for the concentration to decrease from the equilibrium concentration) was calculated.
A vapour atmosphere of the test article was generated and piped to the inlet of the whole body chamber where it was mixed with the chamber supply air. Exhaust atmosphere was filtered (particulate) prior to entering the in-house exhaust system. Test article flow rate = 0.75 mL/min; supply airflow rate 26.9 L/min; chamber ventilation rate = 30.6 L/min.

TEST ATMOSPHERE
- Brief description of analytical method used: Two primary compounds of the test article, DIB-1 (2,4,4-trimethyl-1-pentene) and DIB-2 (2,4,4-trimethyl-2-pentene), were analyzed independently with each sample obtained by gas chromatography.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
4185 ppm
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 and weighing: Mortality - at the approximate midpoint of exposure, immediately following exposure on study day 0 and twice daily thereafter for 14 days; Clinical obs: observed for mortality at the approximate midpoint of exposure, immediately following exposure on study day 0 and twice daily thereafter for 14 days; Bodyweights: Immediately prior to exposure on day 0 and on days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
None (limit test, no mortalities)
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 19 171 mg/m³ air
Remarks on result:
other: >4185 ppm
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4 185 ppm
Remarks on result:
other: No mortalities
Mortality:
No mortalities
Clinical signs:
Clinical observations immediately following exposure included red material around the nose, mouth and eye, white and clear material around the mouth and yellow material on the urogenital area. Yellow material on the urogenital area was noted during the 14-day post-exposure period. Animals were considered normal by study day 3.
Body weight:
There was no effect on bodyweight
Gross pathology:
There were no gross findings for any animals at the scheduled necropsy
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute LC50 of diisobutylene was greater than 4185 ppm when male and female albino rats were exposed via whole-body to a vapour of the test
article for a single, 4-hour period.
Executive summary:

The acute inhalation toxicity of diisobutylene was evaluated in a 4-hour, single exposure study in male and female albino rats. There were no mortalities and no overt signs of toxicity. The acute LC50 of diisobutylene was greater than 4185 ppm, equivalent to 19171 mg/m3 air.

Diisobutylene does not require classification under DSD or CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
19 171 mg/m³
Quality of whole database:
Adequate information is available to characterise the short-term hazards of this substance

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD (remote Sprague-Dawley origin)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England.
- Age at study initiation: not specified (young adult)
- Weight at study initiation (Day -1): 206-224 g (males); 205-218 g (females)
- Fasting period before study: No
- Housing: Stainless steel grid cages. Five animals of the same sex / cage.
- Diet: Complete pelleted rodent diet (RMI(E) SQC, from Special Diets Services Limited, Witham, Essex, England) ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-28°C
- Humidity: 54-70%
- Air changes: at least 10/hr
- Photoperiod: 12 hrs dark / 12 hrs light):

IN-LIFE DATES: From: 11 June 1996 To: 25 June 1996
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 cm x 5 cm of the dorsum
- % coverage: 10%
- Type of wrap if used: 5 cm x 5 cm gauze patch, occluded with aluminium foil. The foil was kept in place and protected by a pad of cotton wool and a
bandage of waterproof plaster and tape wrapped twice around the trunk of the body with sufficient tension to ensure the dose remained securely in place.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Site gently wiped with wet disposable tissues to remove residual test material.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:
24 hours
Doses:
2000 mg/kg (limit dose)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Observations made 3 times during 1st hour after application, 2 further observations during day 1, twice daily thereafter. Bodyweight recorded on the day before dosing and on Days 1, 8 and 15.
- Necropsy of survivors performed: yes (on day 15)
- Other examinations performed: none
Statistics:
Not applicable (limit test, no mortalities)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortalities
Clinical signs:
Systemic signs of reaction to treatment restricted to vocalisation in all animals 15 mins after application of the test material
Body weight:
The animals achieved anticipated bodyweight gains
Gross pathology:
No macroscopic abnormalities
Interpretation of results:
other: low dermal toxicity
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dosage (LD50) of 2,4,4-trimethylpentene was greater than 2000 mg/kg. 2,2,4-trimethyl pentene is considered to be of low dermal toxicity.
Executive summary:

The acute dermal toxicity of 2,4,4-trimethylpentene was assessed in a group of 5 male and 5 female CD rats exposed to 2000 mg/kg under an occlusive dressing for 24 hours. Animals were observed daily and weighed weekly during a 14 days observation period. There were no mortalities and no overt signs of toxicity. The only treatment -related finding was vocalisation in all animals 15 mins after application of the test material.

The acute dermal median lethal dosage (LD50) of 2,4,4-trimethylpentene was greater than 2000 mg/kg. 2,2,4-trimethyl pentene is considered to be of low dermal toxicity and does not require classification under DSD or CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Adequate information is available to characterise the short-term hazards of this substance

Additional information

ACUTE ORAL TOXICITY

The acute oral rat LD50 of 2,4,4-trimethylpentene (purity>95%) was greater than 2000 mg/kg, the limit dose (HLS, 1996 a). No deaths and no clinical signs were observed in this study. However an earlier study, although not documented to current standards, reported clinical findings of transient nervous system effects (Bayer AG (1972).

ACUTE DERMAL TOXICITY

No deaths were observed when a dose of 2000 mg/kg 2,4,4-trimethylpentene (purity>95%) was applied to the skin of rats for 24 hours (HLS, 1996 b). The acute dermal rat LD50 is >2000 mg/kg.

ACUTE INHALATION TOXICITY

There are no acute inhalation data directly available for 2,4,4 -trimethylpentene (purity>95%)). Information for diisobutylene (reduced purity material - about 85%) characterise a substance of low acute inhalation toxicity with acute LC50 greater than 4185 ppm (19171 mg/m3 air) the only concentration tested (WIL, 2006a). 2,4,4 -trimethylpentene is also likely to have low acute toxicity by the inhalation route.


Justification for selection of acute toxicity – oral endpoint
Available information indicates that the acute oral toxicity of this substance is low, and that the LD50 exceeds 2000 mg/kg bw

Justification for selection of acute toxicity – inhalation endpoint
Available information on a related substance (diisobutylene) indicates that the acute inhalation toxicity of this substance is low, and that the LC50 exceeds 19,000 mg/m3

Justification for selection of acute toxicity – dermal endpoint
Available information indicates that the acute dermal toxicity of this substance is low, and that the LD50 exceeds 2000 mg/kg bw

Justification for classification or non-classification

Guideline studies indicate that 2,4,4 -trimethylpentene is of low acute toxicity by the oral and dermal routes with LD50 values exceeding the doses which would warrant classification under GHS/CLP or DSD.

However an earlier study, although not reported to current standards (Bayer, 1972), indicated specific target organ systemic toxicity - single exposure category 3 classification is warranted: CLP GHS:

STOT Single 3 H336.

Aspiration hazard is a known hazard of some hydrocarbons and classification and labelling will depend on the kinematic viscosity (20.5 mm2/s or less for category 1, and of 14 mm2/s or less for category 2 H304 GHS/CLP; DSD Risk phrase R65).