Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20.57 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
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:
no hazard identified
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:
3.87 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
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:
no hazard identified
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

Workers

Chapter 8 of the reach TGD (Appendix R.8 -8) indicates that acute exposure DNEL values are not normally required. Additionally, the lack of acute oral or dermal toxicity for a principal metabolite (1,4 -cyclohexane dicarboxylic acid; CHDA) would indicate that DMCD is non-hazardous under acute exposure scenarios. It is assumed also that there will be no acute or ling-term oral exposures to DMCD in worker populations. Eye and respiratory irritation thresholds are assumed to exceed thresholds for chronic systemic effects.                            

Long-term inhalation, systemic

A 14 -week repeat dose oral toxicity study using CHDA gave a NOEL of 100 mg/kg. Using CHDA data to read-across to DMCD, and extrapolating from subchronic oral toxicity to chronic inhalation, the NOEL first must be converted to mg/m3 by dividing by a factor of 0.38, and then corrected for oral bioavailability (50%) by multiplying by a factor of 2. Further corrections are then necessary to convert from the 6 hour daily exposure to an 8 hour per day exposure (0.75), correction for 7-day experimental exposure to 5-day work week (1.4) and to adjusted for respiration for light work (0.67). ECETOC Assessment factors were applied, which consisted of subchronic to chronic studies (2), for intraspecies (3), for interspecies (4), for a total of 24.     

- Converting mg/kg to mg/m3 = 100/0.38 = 263.16 mg/m3

- Correcting for oral bioavailability = 263.16*2 = 526.32 mg/m3

- Correcting for 7-day experimental exposure to 5-day work week, and light work= 526.32 mg/m3* (1.4) *(0.67) = 493.69 mg/m3

- Application of adjustment factors: 493.69 mg/m3/24 =20.57 mg/m3

Long-term dermal, systemic

A 14 -week repeat dose oral toxicity study using CHDA gave a NOEL of 100 mg/kg. Using CHDA data to read-across to DMCD, and extrapolating from subchronic oral toxicity to chronic dermal, theNOEL first must be corrected to convert from the 6 hour daily exposure to an 8 hour per day exposure (0.75), and correction for 7-day experimental exposure to 5-day work week (1.4) and to adjusted for respiration for light work (0.67). ECETOC Assessment factors were applied, which consisted of subchronic to chronic studies (2), for intraspecies (3), for interspecies (4), for a total of 24.

- Correcting for 7-day experimental exposure to 5-day work week, and light work = 100 mg/kg*(1.4)*(0.67) = 92.96 mg/kg

- Application of adjustment factors: 92.96 mg/kg/24 = 3.87 mg/kg

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.35 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
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:
no hazard identified
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:
2.5 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

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
2.5 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

General Population

Chapter 8 of the reach TGD (Appendix R.8 -8) indicates that acute exposure DNEL values are not normally required. Additionally, the lack of acute oral or dermal toxicity for a principal metabolite (1,4 -cyclohexane dicarboxylic acid; CHDA) would indicate that DMCD is non-hazardous under acute exposure scenarios. It is assumed also that there will be no acute oral exposures to DMCD in general populations. Eye and respiratory irritation thresholds are assumed to exceed thresholds for chronic systemic effects.                          

Long-term inhalation, systemic

A 14 -week repeat dose oral toxicity study using CHDA gave a NOEL of 100 mg/kg. Using these data to read-across to DMCD, and extrapolating from subchronic oral toxicity to chronic inhalation, theNOEL first must be converted to mg/m3by dividing by a factor of 1.15, and then corrected for oral bioavailability (50%) by multiplying by a factor of 2. ECETOC Assessment factors were applied, which consisted of subchronic to chronic studies (2), for intraspecies (5), for interspecies (4), for a total of 40.   

 - Converting mg/kg to mg/m3= 100/1.15 = 86.96 mg/m3

- Correcting for oral bioavailability = 86.96*2 = 173.91 mg/m3

- Application of adjustment factors – 173.91 mg/m3/40 = 4.35 mg/m3

Long-term dermal, systemic

A 14 -week repeat dose oral toxicity study using CHDA gave a NOEL of 100 mg/kg.  These data were used to read-across to DMCD. ECETOC Assessment factors were applied, which consisted of subchronic to chronic studies (2), for intraspecies (5), for interspecies (4), for a total of 40.

- Application of adjustment factors: 100 mg/kg/40 = 2.50 mg/kg

Long-term oral, systemic

A 14 -week repeat dose oral toxicity study using CHDA gave a NOEL of 100 mg/kg. These data were used to read-across to DMCD. ECETOC Assessment factors were applied, which consisted of subchronic to chronic studies (2), for intraspecies (5), for interspecies (4), for a total of 40.

- Application of adjustment factors: 100 mg/kg/40 = 2.50 mg/kg