Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.38 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
83.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
46.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
43.2
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
9
Dose descriptor:
other: LOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The long-term DNELs relevant for workers were based on the key studies below. The assessment factors taken into account are based on the ECETOC information (2010).

A key study for dermal repeated dose administration was performed in rats with Terphenyl, hydrogenated (Monsanto, 1984). Therphenyl, hydrogenated was administered by dermal application to three groups of 10 male and 10 female New Zealand White rabbits, one-half with intact skin and one-half with abraded skin, five days per week for three consecutive weeks at dosage levels of 0, 125, 500 and 2000 mg/kg. One rabbit at the high dosage level (2000 mg/kg) was found dead on study Day 7 and one control rabbit was found dead on study Day 14. A number of incidental and spontaneous signs were noted in the control and test groups. Possible anorexia was observed in an occasional animal in the control, 500 and 2000 mg/kg groups. No statistically significant differences were seen in group mean body weights. Very slight to moderate erythema, edema, atonia, desquamation, coriaceousness and very slight marked fissuring were observed for some rabbits in all test groups. Several animals in all test groups exhibited marked desquamation during the latter part of the study. Blanching (125 and 2000 mg/kg) and subcutaneous hemorrhaging (125 and 500 mg/kg) were observed. No relevant changes were observed for haematology and clinical chemistry. No toxicologically significant test article-related weight variations (absolute or relative) were observed among animals sacrificed at study termination. At macroscopic examination, commonly observed findings were thickening and crust formation of the skin were observed at all dose levels in both sexes. Test article-related histological changes on the skin application sites were observed among all male and female rabbits at all dose levels; consisting of epithelial acanthosis, epidermal hyperkeratosis and inflammatory cell infiltrates among animals sacrificed at study termination.Microabscesses were present at the 2000 mg/kg dosage level. One male animal at 2000 mg/kg dosage level that died on the study, also showed similar type of changes on the skin application site mentioned above. The distribution and relative severity of the above skin changes were generally more pronounced among male and female rabbits at the 2000 mg/kg dosage level. The changes described in tissues other than the skin application sites were regarded as spontaneous in nature, not unusual for rabbits of this age and strain and unrelated to compound application. In conclusion,daily administration of Terphenyl, hydrogenated to the skin of rabbits for 21-days produced gross and microscopic changes at the dosage levels of 125, 500 and 2000 mg/kg/day. There were however no major signs of systemic toxicity;the findings are considered to be related to the dermal application of Terphenyl, hydrogenated; the distribution and severity were generally more pronounced among male and female rabbits at the 2000 mg/kg dose level.

A key study for inhalation repeated dose administration was performed in rats with Therphenyl, hydrogenated (Monsanto, 1986). Therphenyl, hydrogenated when administered by whole-body inhalation exposure as an aerosol to 90 CD (Sprague-Dawley derived) rats (15/sex/group) for six hours per day, five days per week for thirteen weeks at target concentrations of 0, 10, 100 and 500 mg/m³ (groups I, II, III,IV). One Group I female and one Group II female died spontaneously during the study. The Group II female’s death was not considered treatment related. Increased incidences of chromodacryorrhea, excess lacrimation and rough coat were exhibited by all groups of treated males compared to control males. Increased incidences of dried brown material around the facial area were exhibited by all treated groups of females compared to control females. These findings were considered to be treatment related. The mean body weights were decreased approximately 8% for the Group IV males during the study compared to the control males. The differences between Group IV and control males were considered suggestive of a treatment related effect. Although some statistically significant differences were seen at study termination between clinical chemistry values for control and treated groups, values were generally within control ranges and the absence of supporting microscopic lesions or organ weight findings suggests these clinical chemistry results were insufficient to be considered toxicologically significant. The mean absolute and relative liver weights were increased for all groups of treated males compared to control males. The differences between treated and control males were statistically significant for all comparisons except for the absolute liver weights of Group II and III males. Postmortem findings, observed grossly and microscopically, either occurred in the treated and control animals with comparable incidence and severity or they occurred sporadically. These findings did not appear to be related to the test article. The systemic NOAEC was considered to be 100 mg/m³ or 0.1 mg/L air.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
27.8 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.123 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
15
Dose descriptor:
other: LOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The long-term DNELs were based on the key study below (oral DNEL) & on the key studies described in the section for workers (dermal & inhalation DNEL). The assessment factors taken into account are based on the ECETOC information (2010).

 

A key study for oral repeated dose administration was performed in rats with Terphenyl, hydrogenated (Monsanto, 1981). Dosing was performed during  90 days via dietary mixture to 72 Sprague-Dawley CD rats (12/sex/group) at dose levels of 50, 200 and 2000 ppm in the diet for a period of approximately 14 weeks, corresponding with nominal doses of 3, 12 and 120 mg/kg body weight/day. Control animals (12/sex/group) received a standard laboratory diet. All rats survived ; the mean body weights of the high-dose females were slightly lower than control throughout the treatment-period. The mean food consumption values of high-dose males and females were slightly lower than control during the first week of the study and were unremarkable for the remainder of the treatment-period. The high-dose males exhibited slight decrease in mean hemoglobin concentration, hematocrit and erythrocyte counts and a slight increase in mean platelet count. The high-dose males exhibited slight, statistically significant elevations in mean cholesterol and albumin level. The high-dose females exhibited a slight reduction in mean glucose levels. There was an increased incidence of a spontaneously occurring renal tubular lesions in high dose males when compared to control males. The lesion incidence in low and mild dose males was similar to that observed in controls. Females were essentially free of the lesion. The etiology and toxicopathological significance of the increased incidence rate in high dose males was unclear. NOAEL was 200 ppm in the diet, corresponding with 12 mg/kg body weight/day.